% Encoding: UTF-8 @Article{Fraietta2018, author = {Joseph A. Fraietta and Simon F. Lacey and Elena J. Orlando and Iulian Pruteanu-Malinici and Mercy Gohil and Stefan Lundh and Alina C. Boesteanu and Yan Wang and Roddy S. O'Connor and Wei-Ting Hwang and Edward Pequignot and David E. Ambrose and Changfeng Zhang and Nicholas Wilcox and Felipe Bedoya and Corin Dorfmeier and Fang Chen and Lifeng Tian and Harit Parakandi and Minnal Gupta and Regina M. Young and F. Brad Johnson and Irina Kulikovskaya and Li Liu and Jun Xu and Sadik H. Kassim and Megan M. Davis and Bruce L. Levine and Noelle V. Frey and Donald L. Siegel and Alexander C. Huang and E. John Wherry and Hans Bitter and Jennifer L. Brogdon and David L. Porter and Carl H. June and J. Joseph Melenhorst}, title = {Determinants of response and resistance to {CD}19 chimeric antigen receptor ({CAR}) T cell therapy of chronic lymphocytic leukemia}, journal = {Nature Medicine}, year = {2018}, volume = {24}, number = {5}, pages = {563--571}, month = {apr}, doi = {10.1038/s41591-018-0010-1}, publisher = {Springer Nature}, } @Article{Dwarshuis2017, author = {Nate J. Dwarshuis and Kirsten Parratt and Adriana Santiago-Miranda and Krishnendu Roy}, title = {Cells as advanced therapeutics: State-of-the-art, challenges, and opportunities in large scale biomanufacturing of high-quality cells for adoptive immunotherapies}, journal = {Advanced Drug Delivery Reviews}, year = {2017}, volume = {114}, pages = {222--239}, month = {may}, doi = {10.1016/j.addr.2017.06.005}, publisher = {Elsevier {BV}}, } @Article{Fesnak2016, author = {Andrew D. Fesnak and Carl H. June and Bruce L. Levine}, title = {Engineered T cells: the promise and challenges of cancer immunotherapy}, journal = {Nature Reviews Cancer}, year = {2016}, volume = {16}, number = {9}, pages = {566--581}, month = {sep}, doi = {10.1038/nrc.2016.97}, publisher = {Springer Nature}, } @Article{Gattinoni2012, author = {Gattinoni, Luca and Klebanoff, Christopher A and Restifo, Nicholas P}, journal = {Nature reviews. Cancer}, title = {{Paths to stemness: building the ultimate antitumour T cell.}}, year = {2012}, issn = {1474-1768}, month = {oct}, number = {10}, pages = {671--84}, volume = {12}, abstract = {Stem cells are defined by the ability to self-renew and to generate differentiated progeny, qualities that are maintained by evolutionarily conserved pathways that can lead to cancer when deregulated. There is now evidence that these stem cell-like attributes and signalling pathways are also shared among subsets of mature memory T lymphocytes. We discuss how using stem cell-like T cells can overcome the limitations of current adoptive T cell therapies, including inefficient T cell engraftment, persistence and ability to mediate prolonged immune attack. Conferring stemness to antitumour T cells might unleash the full potential of cellular therapies.}, annote = {has good chart of CD8+ T cell differentiation from naive -{\textgreater} stem memory -{\textgreater} central memory -{\textgreater} effector memory -{\textgreater} primary effector a review on the T cell phenotypes most associated with good clinical outcomes in melanoma patients}, doi = {10.1038/nrc3322}, keywords = {.review, Adoptive Transfer, CAR, Cell Differentiation, Hematopoietic Stem Cell Transplantation, Hematopoietic Stem Cells, Hematopoietic Stem Cells: immunology, Humans, Immunologic Memory, Neoplasms, Neoplasms: immunology, Neoplasms: therapy, Signal Transduction, T cell, T-Lymphocytes, T-Lymphocytes: immunology, T-Lymphocytes: transplantation, immunotherapy, stem memory}, mendeley-tags = {.review,CAR,T cell,immunotherapy,stem memory}, pmid = {22996603}, publisher = {Nature Publishing Group, a division of Macmillan Publishers Limited. All Rights Reserved.}, shorttitle = {Nat Rev Cancer}, } @Article{Zheng2012, author = {Zhili Zheng and Nachimuthu Chinnasamy and Richard A Morgan}, title = {Protein L: a novel reagent for the detection of Chimeric Antigen Receptor ({CAR}) expression by flow cytometry}, journal = {Journal of Translational Medicine}, year = {2012}, volume = {10}, number = {1}, pages = {29}, doi = {10.1186/1479-5876-10-29}, publisher = {Springer Nature}, } @Article{Rosenberg2015, author = {S. A. Rosenberg and N. P. Restifo}, title = {Adoptive cell transfer as personalized immunotherapy for human cancer}, journal = {Science}, year = {2015}, volume = {348}, number = {6230}, pages = {62--68}, month = {apr}, doi = {10.1126/science.aaa4967}, publisher = {American Association for the Advancement of Science ({AAAS})}, } @Article{Rosenberg2011, author = {S. A. Rosenberg and J. C. Yang and R. M. Sherry and U. S. Kammula and M. S. Hughes and G. Q. Phan and D. E. Citrin and N. P. Restifo and P. F. Robbins and J. R. Wunderlich and K. E. Morton and C. M. Laurencot and S. M. Steinberg and D. E. White and M. E. Dudley}, title = {Durable Complete Responses in Heavily Pretreated Patients with Metastatic Melanoma Using T-Cell Transfer Immunotherapy}, journal = {Clinical Cancer Research}, year = {2011}, volume = {17}, number = {13}, pages = {4550--4557}, month = {apr}, doi = {10.1158/1078-0432.ccr-11-0116}, publisher = {American Association for Cancer Research ({AACR})}, } @Article{Ghassemi2018, author = {Saba Ghassemi and Selene Nunez-Cruz and Roddy S. O'Connor and Joseph A. Fraietta and Prachi R. Patel and John Scholler and David M. Barrett and Stefan M. Lundh and Megan M. Davis and Felipe Bedoya and Changfeng Zhang and John Leferovich and Simon F. Lacey and Bruce L. Levine and Stephan A. Grupp and Carl H. June and J. Joseph Melenhorst and Michael C. Milone}, title = {{Reducing Ex} {Vivo Culture} Improves the Antileukemic Activity of Chimeric Antigen Receptor ({CAR}) T Cells}, journal = {Cancer Immunology Research}, year = {2018}, volume = {6}, number = {9}, pages = {1100--1109}, month = {jul}, doi = {10.1158/2326-6066.cir-17-0405}, publisher = {American Association for Cancer Research ({AACR})}, } @Article{Kalos2011, author = {Kalos, Michael and Levine, Bruce L and Porter, David L and Katz, Sharyn and Grupp, Stephan a and Bagg, Adam and June, Carl H}, journal = {Science translational medicine}, title = {{T cells with chimeric antigen receptors have potent antitumor effects and can establish memory in patients with advanced leukemia.}}, year = {2011}, issn = {1946-6242}, month = {aug}, number = {95}, pages = {95ra73}, volume = {3}, abstract = {Tumor immunotherapy with T lymphocytes, which can recognize and destroy malignant cells, has been limited by the ability to isolate and expand T cells restricted to tumor-associated antigens. Chimeric antigen receptors (CARs) composed of antibody binding domains connected to domains that activate T cells could overcome tolerance by allowing T cells to respond to cell surface antigens; however, to date, lymphocytes engineered to express CARs have demonstrated minimal in vivo expansion and antitumor effects in clinical trials. We report that CAR T cells that target CD19 and contain a costimulatory domain from CD137 and the T cell receptor $\zeta$ chain have potent non-cross-resistant clinical activity after infusion in three of three patients treated with advanced chronic lymphocytic leukemia (CLL). The engineered T cells expanded {\textgreater}1000-fold in vivo, trafficked to bone marrow, and continued to express functional CARs at high levels for at least 6 months. Evidence for on-target toxicity included B cell aplasia as well as decreased numbers of plasma cells and hypogammaglobulinemia. On average, each infused CAR-expressing T cell was calculated to eradicate at least 1000 CLL cells. Furthermore, a CD19-specific immune response was demonstrated in the blood and bone marrow, accompanied by complete remission, in two of three patients. Moreover, a portion of these cells persisted as memory CAR(+) T cells and retained anti-CD19 effector functionality, indicating the potential of this major histocompatibility complex-independent approach for the effective treatment of B cell malignancies.}, annote = {the paper from Levine/June that includes the CD107a cytotox assay}, doi = {10.1126/scitranslmed.3002842}, groups = {[ndwar:]}, isbn = {1946-6242 (Electronic) 1946-6234 (Linking)}, keywords = {.article, Aged, Antigens, Antigens: immunology, Antineoplastic Agents, Antineoplastic Agents: therapeutic use, Bone Marrow, Bone Marrow: immunology, Bone Marrow: pathology, CAR, CD19, CD19: metabolism, Cell Proliferation, Cytokines, Cytokines: blood, Gene Transfer Techniques, Genetic Vectors, Genetic Vectors: genetics, Humans, Immunologic, Immunologic Memory, Immunologic Memory: immunology, Immunologic: immunology, Leukemia, Leukemia: blood, Leukemia: immunology, Leukemia: pathology, Male, Middle Aged, Neoplasm Staging, Plasma Cells, Plasma Cells: immunology, Plasma Cells: pathology, Receptors, T cell, T-Lymphocytes, T-Lymphocytes: immunology, T-Lymphocytes: pathology, Treatment Outcome, Tumor Burden, Tumor Burden: immunology}, mendeley-tags = {.article,CAR,T cell}, pmid = {21832238}, } @Article{Bashour2015, author = {Bashour, Keenan T and Larson, Ryan P and Graef, Patricia and Stemberger, Christian and Lothar, Germeroth and Odegard, Valerie and Ramsborg, Christopher G}, journal = {Blood}, title = {Functional Characterization of a T Cell Stimulation Reagent for the Production of Therapeutic Chimeric Antigen Receptor T Cells}, year = {2015}, issn = {0006-4971}, number = {23}, pages = {1901--1901}, volume = {126}, abstract = {Adoptive cell therapy using gene-modified T cells has demonstrated promising clinical outcomes in hematologic malignancies. Production of gene-modified T cells involves the selection of patient T cells, activation via stimulation through the endogenous T cell receptor (TCR) complex and a costimulatory domain, followed by introduction of a tumor antigen-specific TCR or chimeric antigen receptor (CAR) through gene modification. Here we characterize a soluble T cell stimulation reagent, known as an ExpamerTM reagent, in the production of therapeutic CAR T cells.The Expamer reagent used in these studies is designed to be a late-stage clinical and commercial manufacturing ancillary material with two important attributes that make it highly attractive from a manufacturing and regulatory standpoint; it is a soluble and dissociable reagent. These attributes increase the ease of both introduction and removal from the manufacturing process, giving products manufactured with this reagent consistent product quality and purity. This reagent activates T cells through the simultaneous engagement of the TCR-CD3 complex and the costimulatory receptor CD28 and is compatible with manufacturing of both current and next-generation therapeutics.Purified healthy donor T cells cultured in the presence of the Expamer reagent rapidly fluxed Ca2+, demonstrating the capacity to induce early TCR signaling. Activation through this reagent additionally promotes upregulation of the cell surface activation marker CD25 and proliferation as measured by CFSE dilution. Following stimulation with this reagent, T cells are readily transduced with a CD19-specific CAR construct. The function of CAR T cells generated with this reagent was measured by effector cytokine production, proliferation, and cytolytic activity in the presence of CD19 expressing and control target cells in vitro. CAR T cells robustly produced IFN-ɣ and IL-2 after activation with a CAR specific antigen. In addition, proliferation in the presence of CD19 expressing target cells was observed as measured by CFSE dilution. Finally, significant cytolytic activity against CD19-expressing target cells was observed.Collectively, these data provide evidence that functional engineered T cells can be manufactured using the Expamer reagent and support implementation into the production of both current and next-generation therapeutic gene-modified T cells.The first two authors contributed equally to this work.Disclosures Bashour: Juno Therapeutics: Employment. Larson: Juno Therapeutics: Employment. Graef: Juno Therapeutics: Employment. Stemberger: Juno Therapeutics: Employment. Lothar: Juno Therapeutics: Employment. Odegard: Juno Therapeutics: Employment. Ramsborg: Juno Therapeutics: Employment.↵* Asterisk with author names denotes non-ASH members.}, groups = {ndwar:6}, publisher = {American Society of Hematology}, } @Article{Adachi2018, author = {Keishi Adachi and Yosuke Kano and Tomohiko Nagai and Namiko Okuyama and Yukimi Sakoda and Koji Tamada}, title = {{IL}-7 and {CCL}19 expression in {CAR}-T cells improves immune cell infiltration and {CAR}-T cell survival in the tumor}, journal = {Nature Biotechnology}, year = {2018}, volume = {36}, number = {4}, pages = {346--351}, month = {mar}, doi = {10.1038/nbt.4086}, publisher = {Springer Nature}, } @Article{Baldan2015, author = {V Baldan and R Griffiths and R E Hawkins and D E Gilham}, title = {Efficient and reproducible generation of tumour-infiltrating lymphocytes for renal cell carcinoma}, journal = {British Journal of Cancer}, year = {2015}, volume = {112}, number = {9}, pages = {1510--1518}, month = {mar}, doi = {10.1038/bjc.2015.96}, publisher = {Springer Nature}, } @Article{Bank1994, author = {Ilan Bank and Mazal Book and Randle Ware}, title = {Functional Role of {VLA}-1 ({CD}49A) in Adhesion, Cation-Dependent Spreading, and Activation of Cultured Human T Lymphocytes}, journal = {Cellular Immunology}, year = {1994}, volume = {156}, number = {2}, pages = {424--437}, month = {jul}, doi = {10.1006/cimm.1994.1187}, publisher = {Elsevier {BV}}, } @Article{Ben-Horin2004, author = {Shomron Ben-Horin and Ilan Bank}, title = {The role of very late antigen-1 in immune-mediated inflammation}, journal = {Clinical Immunology}, year = {2004}, volume = {113}, number = {2}, pages = {119--129}, month = {nov}, doi = {10.1016/j.clim.2004.06.007}, publisher = {Elsevier {BV}}, } @Article{Besser2010, author = {M. J. Besser and R. Shapira-Frommer and A. J. Treves and D. Zippel and O. Itzhaki and L. Hershkovitz and D. Levy and A. Kubi and E. Hovav and N. Chermoshniuk and B. Shalmon and I. Hardan and R. Catane and G. Markel and S. Apter and A. Ben-Nun and I. Kuchuk and A. Shimoni and A. Nagler and J. Schachter}, title = {Clinical Responses in a Phase {II} Study Using Adoptive Transfer of Short-term Cultured Tumor Infiltration Lymphocytes in Metastatic Melanoma Patients}, journal = {Clinical Cancer Research}, year = {2010}, volume = {16}, number = {9}, pages = {2646--2655}, month = {apr}, doi = {10.1158/1078-0432.ccr-10-0041}, publisher = {American Association for Cancer Research ({AACR})}, } @Article{Blanc2018, author = {Charlotte Blanc and Sophie Hans and Thi Tran and Clemence Granier and Antonin Saldman and Marie Anson and Stephane Oudard and Eric Tartour}, title = {Targeting Resident Memory T Cells for Cancer Immunotherapy}, journal = {Frontiers in Immunology}, year = {2018}, volume = {9}, month = {jul}, doi = {10.3389/fimmu.2018.01722}, publisher = {Frontiers Media {SA}}, } @Article{Boisvert2007, author = {Marc Boisvert and Steve Gendron and Nizar Chetoui and Fawzi Aoudjit}, title = {Alpha2beta1 integrin signaling augments T cell receptor-dependent production of interferon-gamma in human T cells}, journal = {Molecular Immunology}, year = {2007}, volume = {44}, number = {15}, pages = {3732--3740}, month = {jul}, doi = {10.1016/j.molimm.2007.04.003}, publisher = {Elsevier {BV}}, } @Article{Brimnes2012, author = {Marie Klinge Brimnes and Anne Ortved Gang and Marco Donia and Per thor Straten and Inge Marie Svane and Sine Reker Hadrup}, title = {Generation of autologous tumor-specific T cells for adoptive transfer based on vaccination, in vitro restimulation and {CD}3/{CD}28 dynabead-induced T cell expansion}, journal = {Cancer Immunology, Immunotherapy}, year = {2012}, volume = {61}, number = {8}, pages = {1221--1231}, month = {jan}, doi = {10.1007/s00262-011-1199-8}, publisher = {Springer Nature}, } @Article{Buck2016, author = {Buck, Michael D. and O'Sullivan, David and {Klein Geltink}, Ramon I. and Curtis, Jonathan D. and Chang, ChihHao and Sanin, David E. and Qiu, Jing and Kretz, Oliver and Braas, Daniel and van der Windt, Gerritje J.W. and Chen, Qiongyu and Huang, Stanley Ching-Cheng and O'Neill, Christina M. and Edelson, Brian T. and Pearce, Edward J. and Sesaki, Hiromi and Huber, Tobias B. and Rambold, Angelika S. and Pearce, Erika L.}, journal = {Cell}, title = {{Mitochondrial Dynamics Controls T Cell Fate through Metabolic Programming}}, year = {2016}, issn = {00928674}, month = {jun}, pages = {114}, volume = {166}, abstract = {Activated effector T (TE) cellsaugment anabolic path- ways of metabolism, such as aerobic glycolysis, while memory T (TM) cells engage catabolic path- ways, like fatty acid oxidation (FAO). However, sig- nals that drive these differences remain unclear. Mitochondria are metabolic organelles that actively transform their ultrastructure. Therefore, we ques- tioned whether mitochondrial dynamics controls T cell metabolism. We show that TE cells have punc- tate mitochondria, while TM cells maintain fused net- works. The fusion protein Opa1 is required for TM, but not TE cells after infection, and enforcing fusion in TE cells imposes TM cell characteristics and enhances antitumor function. Our data suggest that, by altering cristae morphology, fusion in TM cells configures electron transport chain (ETC) complex associations favoring oxidative phosphorylation (OXPHOS) and FAO, while fission in TE cells leads to cristae expan- sion, reducing ETC efficiency and promoting aerobic glycolysis. Thus, mitochondrial remodeling is a signaling mechanism that instructs T cell metabolic programming.}, doi = {10.1016/j.cell.2016.05.035}, groups = {[ndwar:]}, keywords = {.article, T cell, metabolism}, mendeley-tags = {.article,T cell,metabolism}, } @Article{Cheung2018, author = {Cheung, Alexander S. and Zhang, David K. Y. and Koshy, Sandeep T. and Mooney, David J.}, title = {Scaffolds that mimic antigen-presenting cells enable ex vivo expansion of primary {T} cells}, journal = {Nature Biotechnology}, year = {2018}, volume = {36}, number = {2}, pages = {160--169}, month = {jan}, doi = {10.1038/nbt.4047}, publisher = {Springer Nature}, } @Article{Cho2015, author = {Hyun-Woo Cho and Su-Yeon Kim and Dae-Hee Sohn and Min-Ji Lee and Mi-Young Park and Hyun-Jung Sohn and Hyun-Il Cho and Tai-Gyu Kim}, title = {Triple costimulation via {CD}80, 4-1BB, and {CD}83 ligand elicits the long-term growth of V$\upgamma$9V$\updelta$2 T cells in low levels of {IL}-2}, journal = {Journal of Leukocyte Biology}, year = {2015}, volume = {99}, number = {4}, pages = {521--529}, month = {nov}, doi = {10.1189/jlb.1hi0814-409rr}, publisher = {Wiley}, } @Article{Couzin-Frankel2017, author = {Jennifer Couzin-Frankel}, title = {Supply of promising T cell therapy is strained}, journal = {Science}, year = {2017}, volume = {356}, number = {6343}, pages = {1112--1113}, month = {jun}, doi = {10.1126/science.356.6343.1112}, publisher = {American Association for the Advancement of Science ({AAAS})}, } @Article{DSouza2006, author = {W. N. {D'Souza} and S. M. Hedrick}, title = {Cutting Edge: Latecomer {CD}8 T Cells Are Imprinted with a Unique Differentiation Program}, journal = {The Journal of Immunology}, year = {2006}, volume = {177}, number = {2}, pages = {777--781}, month = {jul}, doi = {10.4049/jimmunol.177.2.777}, publisher = {The American Association of Immunologists}, } @Article{Delalat2017, author = {Delalat, Bahman and Harding, Frances and Gundsambuu, Batjargal and De-Juan-Pardo, Elena M. and Wunner, Felix M. and Wille, Marie Luise and Jasieniak, Marek and Malatesta, Kristen A.L. and Griesser, Hans J. and Simula, Antonio and Hutmacher, Dietmar W. and Voelcker, Nicolas H. and Barry, Simon C.}, journal = {Biomaterials}, title = {{3D printed lattices as an activation and expansion platform for T cell therapy}}, year = {2017}, issn = {18785905}, pages = {58--68}, volume = {140}, abstract = {One of the most significant hurdles to the affordable, accessible delivery of cell therapy is the cost and difficulty of expanding cells to clinically relevant numbers. Immunotherapy to prevent autoimmune disease, tolerate organ transplants or target cancer critically relies on the expansion of specialized T cell populations. We have designed 3D-printed cell culture lattices with highly organized micron-scale architectures, functionalized via plasma polymerization to bind monoclonal antibodies that trigger cell proliferation. This 3D technology platform facilitate the expansion of therapeutic human T cell subsets, including regulatory, effector, and cytotoxic T cells while maintaining the correct phenotype. Lentiviral gene delivery to T cells is enhanced in the presence of the lattices. Incorporation of the lattice format into existing cell culture vessels such as the G-Rex system is feasible. This cell expansion platform is user-friendly and expedites cell recovery and scale-up, making it ideal for translating T cell therapies from bench to bedside.}, doi = {10.1016/j.biomaterials.2017.05.009}, keywords = {.article, 3D lattice, Cell therapy manufacturing, Immunotherapy, Melt electrospin writing, Plasma polymer functionalization, T cell, biomanufacturing}, mendeley-tags = {.article,T cell,biomanufacturing}, publisher = {Elsevier Ltd}, } @Article{Forget2014, author = {Marie-Andr{\'{e}}e Forget and Shruti Malu and Hui Liu and Christopher Toth and Sourindra Maiti and Charuta Kale and Cara Haymaker and Chantale Bernatchez and Helen Huls and Ena Wang and Francesco M. Marincola and Patrick Hwu and Laurence J.N. Cooper and Laszlo G. Radvanyi}, title = {Activation and Propagation of Tumor-infiltrating Lymphocytes on Clinical-grade Designer Artificial Antigen-presenting Cells for Adoptive Immunotherapy of Melanoma}, journal = {Journal of Immunotherapy}, year = {2014}, volume = {37}, number = {9}, pages = {448--460}, doi = {10.1097/cji.0000000000000056}, publisher = {Ovid Technologies (Wolters Kluwer Health)}, } @Article{Gargett2015, author = {Tessa Gargett and Michael P. Brown}, title = {Different cytokine and stimulation conditions influence the expansion and immune phenotype of third-generation chimeric antigen receptor T~cells specific for tumor antigen {GD}2}, journal = {Cytotherapy}, year = {2015}, volume = {17}, number = {4}, pages = {487--495}, month = {apr}, doi = {10.1016/j.jcyt.2014.12.002}, publisher = {Elsevier {BV}}, } @Article{Gattinoni2011, author = {Luca Gattinoni and Enrico Lugli and Yun Ji and Zoltan Pos and Chrystal M Paulos and M{\'{a}}ire F Quigley and Jorge R Almeida and Emma Gostick and Zhiya Yu and Carmine Carpenito and Ena Wang and Daniel C Douek and David A Price and Carl H June and Francesco M Marincola and Mario Roederer and Nicholas P Restifo}, title = {A human memory T cell subset with stem cell{\textendash}like properties}, journal = {Nature Medicine}, year = {2011}, volume = {17}, number = {10}, pages = {1290--1297}, month = {sep}, doi = {10.1038/nm.2446}, publisher = {Springer Nature}, } @Article{Gendron2003, author = {Steve Gendron and Julie Couture and Fawzi Aoudjit}, title = {Integrin $\alpha$2$\beta$1Inhibits Fas-mediated Apoptosis in T Lymphocytes by Protein Phosphatase 2A-dependent Activation of the {MAPK}/{ERK} Pathway}, journal = {Journal of Biological Chemistry}, year = {2003}, volume = {278}, number = {49}, pages = {48633--48643}, month = {sep}, doi = {10.1074/jbc.m305169200}, publisher = {American Society for Biochemistry {\&} Molecular Biology ({ASBMB})}, } @Article{Gerdemann2011, author = {Gerdemann, Ulrike and Vera, Juan F and Rooney, Cliona M and Leen, Ann M}, journal = {Journal of visualized experiments : JoVE}, title = {{Generation of multivirus-specific T cells to prevent/treat viral infections after allogeneic hematopoietic stem cell transplant.}}, year = {2011}, issn = {1940-087X}, month = {jan}, number = {51}, abstract = {Viral infections cause morbidity and mortality in allogeneic hematopoietic stem cell transplant (HSCT) recipients. We and others have successfully generated and infused T-cells specific for Epstein Barr virus (EBV), cytomegalovirus (CMV) and Adenovirus (Adv) using monocytes and EBV-transformed lymphoblastoid cell (EBV-LCL) gene-modified with an adenovirus vector as antigen presenting cells (APCs). As few as 2x10(5)/kg trivirus-specific cytotoxic T lymphocytes (CTL) proliferated by several logs after infusion and appeared to prevent and treat even severe viral disease resistant to other available therapies. The broader implementation of this encouraging approach is limited by high production costs, complexity of manufacture and the prolonged time (4-6 weeks for EBV-LCL generation, and 4-8 weeks for CTL manufacture--total 10-14 weeks) for preparation. To overcome these limitations we have developed a new, GMP-compliant CTL production protocol. First, in place of adenovectors to stimulate T-cells we use dendritic cells (DCs) nucleofected with DNA plasmids encoding LMP2, EBNA1 and BZLF1 (EBV), Hexon and Penton (Adv), and pp65 and IE1 (CMV) as antigen-presenting cells. These APCs reactivate T cells specific for all the stimulating antigens. Second, culture of activated T-cells in the presence of IL-4 (1,000 U/ml) and IL-7 (10 ng/ml) increases and sustains the repertoire and frequency of specific T cells in our lines. Third, we have used a new, gas permeable culture device (G-Rex) that promotes the expansion and survival of large cell numbers after a single stimulation, thus removing the requirement for EBV-LCLs and reducing technician intervention. By implementing these changes we can now produce multispecific CTL targeting EBV, CMV, and Adv at a cost per 10(6) cells that is reduced by {\textgreater}90{\%}, and in just 10 days rather than 10 weeks using an approach that may be extended to additional protective viral antigens. Our FDA-approved approach should be of value for prophylactic and treatment applications for high risk allogeneic HSCT recipients.}, annote = {a protocol that demonstrated the G-Rex used to make virus-specific T cells}, doi = {10.3791/2736}, groups = {[ndwar:]}, keywords = {.protocol, Antigen-Presenting Cells, Antigen-Presenting Cells: immunology, Dendritic Cells, Dendritic Cells: immunology, Epitopes, T-Lymphocyte, T-Lymphocyte: immunology, Hematopoietic Stem Cell Transplantation, Hematopoietic Stem Cell Transplantation: adverse e, Hematopoietic Stem Cell Transplantation: methods, Humans, Immunotherapy, Adoptive, Adoptive: methods, Lymphocyte Activation, T cell, T-Lymphocytes, Cytotoxic, Cytotoxic: immunology, Virus Diseases, Virus Diseases: etiology, Virus Diseases: immunology, Virus Diseases: prevention {\&} control, Virus Diseases: therapy, biomanufacturing}, mendeley-tags = {.protocol,T cell,biomanufacturing}, pmid = {21654628}, } @Article{Gomez_Eerland_2014, author = {Raquel Gomez-Eerland and Bastiaan Nuijen and Bianca Heemskerk and Nienke van Rooij and Joost H. van den Berg and Jos H. Beijnen and Wolfgang Uckert and Pia Kvistborg and Ton N. Schumacher and John B.A.G. Haanen and Annelies Jorritsma}, title = {Manufacture of Gene-Modified Human T-Cells with a Memory Stem/Central Memory Phenotype}, journal = {Human Gene Therapy Methods}, year = {2014}, volume = {25}, number = {5}, pages = {277--287}, month = {oct}, doi = {10.1089/hgtb.2014.004}, publisher = {Mary Ann Liebert Inc}, } @Article{Harrison2019, author = {Richard P. Harrison and Ezequiel Zylberberg and Simon Ellison and Bruce L. Levine}, title = {Chimeric antigen receptor{\textendash}T cell therapy manufacturing: modelling the effect of offshore production on aggregate cost of goods}, journal = {Cytotherapy}, year = {2019}, month = {feb}, doi = {10.1016/j.jcyt.2019.01.003}, publisher = {Elsevier {BV}}, } @Article{Heathman2015, author = {Thomas R. J. Heathman and Veronica A. M. Glyn and Andrew Picken and Qasim A. Rafiq and Karen Coopman and Alvin W. Nienow and Bo Kara and Christopher J. Hewitt}, title = {Expansion, harvest and cryopreservation of human mesenchymal stem cells in a serum-free microcarrier process}, journal = {Biotechnology and Bioengineering}, year = {2015}, volume = {112}, number = {8}, pages = {1696--1707}, month = {apr}, doi = {10.1002/bit.25582}, publisher = {Wiley}, } @Article{Hickey2017, author = {John W. Hickey and Fernando P. Vicente and Gregory P. Howard and Hai-Quan Mao and Jonathan P. Schneck}, title = {Biologically Inspired Design of Nanoparticle Artificial Antigen-Presenting Cells for Immunomodulation}, journal = {Nano Letters}, year = {2017}, volume = {17}, number = {11}, pages = {7045--7054}, month = {oct}, doi = {10.1021/acs.nanolett.7b03734}, publisher = {American Chemical Society ({ACS})}, } @Manual{stargazer, title = {stargazer: Well-Formatted Regression and Summary Statistics Tables}, author = {Marek Hlavac}, organization = {Central European Labour Studies Institute (CELSI)}, address = {Bratislava, Slovakia}, year = {2018}, note = {R package version 5.2.2}, } @Article{Hromas1997, author = {Hromas, R and Gray, P W and Chantry, D and Godiska, R and Krathwohl, M and Fife, K and Bell, G I and Takeda, J and Aronica, S and Gordon, M and Cooper, S and Broxmeyer, H E and Klemsz, M J}, journal = {Blood}, title = {Cloning and characterization of exodus, a novel beta-chemokine.}, year = {1997}, issn = {0006-4971}, month = may, pages = {3315--3322}, volume = {89}, abstract = {Chemokines are a family of related proteins that regulate leukocyte infiltration into inflamed tissue. Some chemokines such as MIP-1 alpha also inhibit hematopoietic progenitor cell proliferation. Recently, three chemokines, MIP-1 alpha, MIP-1 beta, and RANTES, have been found to significantly decrease human immunodeficiency virus production from infected T cells. We report here the cloning and characterization of a novel human chemokine termed Exodus for its chemotactic properties. This novel chemokine is distantly related to other chemokines (28% homology with MIP-1 alpha) and shares several biological activities. Exodus is expressed preferentially in lymphocytes and monocytes, and its expression is markedly upregulated by mediators of inflammation such as tumor necrosis factor or lipopolysaccharide. Purified synthetic Exodus was found to inhibit proliferation of myeloid progenitors in colony formation assays. Exodus also stimulated chemotaxis of peripheral blood mononuclear cells. The sequence homology, expression, and biological activity indicate that Exodus represents a novel divergent beta-chemokine.}, chemicals = {CCL20 protein, human, CCR6 protein, human, Chemokine CCL20, Chemokines, Chemokines, CC, DNA, Complementary, Macrophage Inflammatory Proteins, Receptors, CCR6, Receptors, Chemokine, Recombinant Proteins}, citation-subset = {AIM, IM, X}, completed = {1997-06-03}, country = {United States}, issn-linking = {0006-4971}, issue = {9}, keywords = {Amino Acid Sequence; Base Sequence; Blotting, Northern; Bone Marrow Cells; Cell Line; Chemokine CCL20; Chemokines, biosynthesis, chemistry, pharmacology; Chemokines, CC; Chemotaxis, drug effects; Cloning, Molecular; DNA, Complementary; Gene Library; Hematopoietic Stem Cells, cytology, drug effects, physiology; Humans; Islets of Langerhans, metabolism; Kinetics; Macrophage Inflammatory Proteins; Molecular Sequence Data; Organ Specificity; Receptors, CCR6; Receptors, Chemokine; Recombinant Proteins, pharmacology; Sequence Homology, Amino Acid; Transcription, Genetic; Tumor Cells, Cultured}, nlm-id = {7603509}, owner = {NLM}, pmid = {9129037}, pubmodel = {Print}, pubstatus = {ppublish}, revised = {2007-11-15}, } @Article{Jin2012, author = {Jin, Jianjian and Sabatino, Marianna and Somerville, Robert and Wilson, John R and Dudley, Mark E and Stroncek, David F and Rosenberg, Steven A}, journal = {Journal of immunotherapy (Hagerstown, Md. : 1997)}, title = {{Simplified method of the growth of human tumor infiltrating lymphocytes in gas-permeable flasks to numbers needed for patient treatment.}}, year = {2012}, issn = {1537-4513}, month = {apr}, number = {3}, pages = {283--92}, volume = {35}, abstract = {Adoptive cell therapy of metastatic melanoma with autologous tumor infiltrating lymphocytes (TIL) is clinically effective, but TIL production can be challenging. Here we describe a simplified method for initial TIL culture and rapid expansion in gas-permeable flasks. TIL were initially cultured from tumor digests and fragments in 40 mL capacity flasks with a 10 cm² gas-permeable silicone bottom, G-Rex10. A TIL rapid expansion protocol (REP) was developed using 500 mL capacity flasks with a 100 cm² gas-permeable silicone bottom, G-Rex100. TIL growth was successfully initiated in G-Rex10 flasks from tumor digests from 13 of 14 patients and from tumor fragments in all 11 tumor samples tested. TIL could then be expanded to 8-10×10⁹ cells in a 2-step REP that began by seeding 5×10⁶ TIL into a G-Rex100 flask, followed by expansion at day 7 into 3 G-Rex100 flasks. To obtain the 30-60×10⁹ cells used for patient treatment, we seeded 6 G-Rex100 flasks with 5×10⁶ cells and expanded into 18 G-Rex100 flasks. Large-scale TIL REP in gas-permeable flasks requires approximately 9-10 L of media, about 3-4 times less than other methods. In conclusion, TIL initiation and REP in gas-permeable G-Rex flasks require fewer total vessels, less media, less incubator space, and less labor than initiation and REP in 24-well plates, tissue culture flasks, and bags. TIL culture in G-Rex flasks will facilitate the production of TIL at the numbers required for patient treatment at most cell processing laboratories.}, annote = {this study developed a simpler TIL growth method using closed system with G-Rex flasks and the young TIL method Advantages of this protocol 1) 4 fold media reduction compared to bag or flask method 2) TILs can be grown from tumor fragments that are not digested or mechanically disrupted, reducing labor 3) only 18 G-Rex flasks needed for 25-60e9 cells (compared to 30-50 flasks or 15-30 bags) 4) less incubator space 5) less labor Disadvantages: 1) not fully closed system 2) no visualization}, doi = {10.1097/CJI.0b013e31824e801f}, groups = {[ndwar:]}, keywords = {.article, Humans, Immunotherapy, Adoptive, Lymphocytes, Tumor-Infiltrating, Tumor-Infiltrating: cytology, Primary Cell Culture, Primary Cell Culture: instrumentation, Primary Cell Culture: methods, Primary Cell Culture: standards, T cell, TIL, biomanufacturing}, mendeley-tags = {.article,T cell,TIL,biomanufacturing}, pmid = {22421946}, } @Article{Joshi2008, author = {N. S. Joshi and S. M. Kaech}, title = {Effector {CD}8 T Cell Development: A Balancing Act between Memory Cell Potential and Terminal Differentiation}, journal = {The Journal of Immunology}, year = {2008}, volume = {180}, number = {3}, pages = {1309--1315}, month = {jan}, doi = {10.4049/jimmunol.180.3.1309}, publisher = {The American Association of Immunologists}, } @Article{kaartinen17, author = {Tanja Kaartinen and Annu Luostarinen and Pilvi Maliniemi and Joni Keto and Mikko Arvas and Heini Belt and Jonna Koponen and Angelica Loskog and Satu Mustjoki and Kimmo Porkka and Seppo Yl{\"a}-Herttuala and Matti Korhonen}, title = {Low Interleukin-2 Concentration Favors Generation of Early Memory T Cells Over Effector Phenotypes During Chimeric Antigen Receptor T-Cell Expansion}, journal = {Cytotherapy}, year = {2017}, volume = {19}, number = {6}, pages = {689-702}, date_added = {Fri Feb 15 13:22:34 2019}, doi = {10.1016/j.jcyt.2017.03.067}, } @Article{Lalor2016, author = {Stephen J. Lalor and Rachel M. McLoughlin}, title = {Memory $\upgamma$$\updelta$ T Cells{\textendash}Newly Appreciated Protagonists in Infection and Immunity}, journal = {Trends in Immunology}, year = {2016}, volume = {37}, number = {10}, pages = {690--702}, month = {oct}, doi = {10.1016/j.it.2016.07.006}, publisher = {Elsevier {BV}}, } @Article{Lambert2017, author = {Lambert, Lester H. and Goebrecht, Geraldine K. E. and {De Leo}, Sarah E. and O'Connor, Roddy S and Nunez-Cruz, Selene and Li, Tai-De and Yuan, Jinglun and Milone, Michael C. and Kam, Lance C.}, journal = {Nano letters}, title = {{Improving T Cell Expansion with a Soft Touch.}}, year = {2017}, issn = {1530-6992}, month = {feb}, number = {2}, pages = {821--826}, volume = {17}, abstract = {Protein-coated microbeads provide a consistent approach for activating and expanding populations of T cells for immunotherapy but do not fully capture the properties of antigen presenting cells. In this report, we enhance T cell expansion by replacing the conventional, rigid bead with a mechanically soft elastomer. Polydimethylsiloxane (PDMS) was prepared in a microbead format and modified with activating antibodies to CD3 and CD28. A total of three different formulations of PDMS provided an extended proliferative phase in both CD4(+)-only and mixed CD4(+)-CD8(+) T cell preparations. CD8(+) T cells retained cytotoxic function, as measured by a set of biomarkers (perforin production, LAMP2 mobilization, and IFN-$\gamma$ secretion) and an in vivo assay of targeted cell killing. Notably, PDMS beads presented a nanoscale polymer structure and higher rigidity than that associated with conventional bulk material. These data suggest T cells respond to this higher rigidity, indicating an unexpected effect of curing conditions. Together, these studies demonstrate that adopting mechanobiology ideas into the bead platform can provide new tools for T cell based immunotherapy.}, doi = {10.1021/acs.nanolett.6b04071}, keywords = {.article, T cell, immunotherapy, mechanobiology, nanoscale rigidity}, mendeley-tags = {.article,T cell}, pmid = {28122453}, } @Article{Lamers2014, author = {Lamers, Cor H J and van Steenbergen-Langeveld, Sabine and van Brakel, Mandy and {Groot-van Ruijven}, Corrien M. and van Elzakker, Pascal M M L and van Krimpen, Brigitte and Sleijfer, Stefan and Debets, Reno}, journal = {Human gene therapy methods}, title = {{T cell receptor-engineered T cells to treat solid tumors: T cell processing toward optimal T cell fitness.}}, year = {2014}, issn = {1946-6544}, month = {dec}, number = {6}, pages = {345--57}, volume = {25}, abstract = {Therapy with autologous T cells that have been gene-engineered to express chimeric antigen receptors (CAR) or T cell receptors (TCR) provides a feasible and broadly applicable treatment for cancer patients. In a clinical study in advanced renal cell carcinoma (RCC) patients with CAR T cells specific for carbonic anhydrase IX (CAIX), we observed toxicities that (most likely) indicated in vivo function of CAR T cells as well as low T cell persistence and clinical response rates. The latter observations were confirmed by later clinical trials in other solid tumor types and other gene-modified T cells. To improve the efficacy of T cell therapy, we have redefined in vitro conditions to generate T cells with young phenotype, a key correlate with clinical outcome. For their impact on gene-modified T cell phenotype and function, we have tested various anti-CD3/CD28 mAb-based T cell activation and expansion conditions as well as several cytokines prior to and/or after gene transfer using two different receptors: CAIX CAR and MAGE-C2(ALK)/HLA-A2 TCR. In a total set of 16 healthy donors, we observed that T cell activation with soluble anti-CD3/CD28 mAbs in the presence of both IL15 and IL21 prior to TCR gene transfer resulted in enhanced proportions of gene-modified T cells with a preferred in vitro phenotype and better function. T cells generated according to these processing methods demonstrated enhanced binding of pMHC, and an enhanced proportion of CD8+, CD27+, CD62L+, CD45RA+T cells. These new conditions will be translated into a GMP protocol in preparation of a clinical adoptive therapy trial to treat patients with MAGE-C2-positive tumors.}, annote = {contains some info on where to find soluble anti-CD3/CD28 for expansion/activation company for soluble Abs = Cilag or Miltenyi ("functional grade") functional grade = low endotoxin, safe buffers, no azides (eg wont kill cells) sCD3 = soluble CD3 bCD3 + 28= MACSiBEAD coated CD3 and CD28}, doi = {10.1089/hgtb.2014.051}, groups = {[ndwar:]}, keywords = {.article, CAR, T cell, expansion, solid tumor}, mendeley-tags = {.article,CAR,T cell,expansion,solid tumor}, pmid = {25423330}, } @Article{Matic2013, author = {Matic, Jovana and Deeg, Janosch and Scheffold, Alexander and Goldstein, Itamar and Spatz, Joachim P.}, journal = {Nano letters}, title = {{Fine tuning and efficient T cell activation with stimulatory aCD3 nanoarrays.}}, year = {2013}, issn = {1530-6992}, month = {nov}, number = {11}, pages = {5090--7}, volume = {13}, abstract = {Anti-CD3 (aCD3) nanoarrays fabricated by self-assembled nanopatterning combined with site-directed protein immobilization techniques represent a novel T cell stimulatory platform that allows tight control over ligand orientation and surface density. Here, we show that activation of primary human CD4+ T cells, defined by CD69 upregulation, IL-2 production and cell proliferation, correlates with aCD3 density on nanoarrays. Immobilization of aCD3 through nanopatterning had two effects: cell activation was significantly higher on these surfaces than on aCD3-coated plastics and allowed unprecedented fine-tuning of T cell response.}, annote = {cool method, but seems like there's an underwhelmingly low amount of data here. what happens to the phenotype of these cells as the ligand density changes? These are problably more important questions to answer for biomanufacturing purposes :)}, doi = {10.1021/nl4022623}, keywords = {.article, T cell, act, anti-cd3 monoclonal antibody, arti fi cial antigen, bcml, block copolymer micellar nanolithography, cd4, doptive cell therapy, is a promising medical, nanopattern, of cancer and chronic, presenting interfaces, signaling, strategy for the treatment, t cell activation, t cells, viral}, mendeley-tags = {.article,T cell,signaling}, pmid = {24111628}, } @Article{meyer15_immun, author = {Randall A. Meyer and Joel C. Sunshine and Karlo Perica and Alyssa K. Kosmides and Kent Aje and Jonathan P. Schneck and Jordan J. Green}, title = {Immunoengineering: Biodegradable Nanoellipsoidal Artificial Antigen Presenting Cells for Antigen Specific T-Cell Activation (Small 13/2015)}, journal = {Small}, year = {2015}, volume = {11}, number = {13}, pages = {1612-1612}, date_added = {Fri Feb 8 22:38:01 2019}, doi = {10.1002/smll.201570077}, } @Article{Milone2009, author = {Michael C. Milone and Jonathan D. Fish and Carmine Carpenito and Richard G. Carroll and Gwendolyn K. Binder and David Teachey and Minu Samanta and Mehdi Lakhal and Brian Gloss and Gwenn Danet-Desnoyers and Dario Campana and James L. Riley and Stephan A. Grupp and Carl H. June}, title = {Chimeric Receptors Containing {CD}137 Signal Transduction Domains Mediate Enhanced Survival of T Cells and Increased Antileukemic Efficacy In Vivo}, journal = {Molecular Therapy}, year = {2009}, volume = {17}, number = {8}, pages = {1453--1464}, month = {aug}, doi = {10.1038/mt.2009.83}, publisher = {Elsevier {BV}}, } @Article{Ohtani2008, author = {Osamu Ohtani and Yuko Ohtani}, title = {Structure and function of rat lymph nodes}, journal = {Archives of Histology and Cytology}, year = {2008}, volume = {71}, number = {2}, pages = {69--76}, doi = {10.1679/aohc.71.69}, publisher = {International Society of Histology {\&} Cytology}, } @Article{Piscopo2017, author = {Nicole J. Piscopo and Katherine P. Mueller and Amritava Das and Peiman Hematti and William L. Murphy and Sean P. Palecek and Christian M. Capitini and Krishanu Saha}, title = {Bioengineering Solutions for Manufacturing Challenges in {CAR} T Cells}, journal = {Biotechnology Journal}, year = {2017}, volume = {13}, number = {2}, pages = {1700095}, month = {sep}, doi = {10.1002/biot.201700095}, publisher = {Wiley}, } @Article{Rao2000, author = {W. H. Rao and J. M. Hales and R. D. R. Camp}, title = {Potent Costimulation of Effector T Lymphocytes by Human Collagen Type I}, journal = {The Journal of Immunology}, year = {2000}, volume = {165}, number = {9}, pages = {4935--4940}, month = {nov}, doi = {10.4049/jimmunol.165.9.4935}, publisher = {The American Association of Immunologists}, } @Article{Robbins2011, author = {Paul F. Robbins and Richard A. Morgan and Steven A. Feldman and James C. Yang and Richard M. Sherry and Mark E. Dudley and John R. Wunderlich and Azam V. Nahvi and Lee J. Helman and Crystal L. Mackall and Udai S. Kammula and Marybeth S. Hughes and Nicholas P. Restifo and Mark Raffeld and Chyi-Chia Richard Lee and Catherine L. Levy and Yong F. Li and Mona El-Gamil and Susan L. Schwarz and Carolyn Laurencot and Steven A. Rosenberg}, title = {Tumor Regression in Patients With Metastatic Synovial Cell Sarcoma and Melanoma Using Genetically Engineered Lymphocytes Reactive With {NY}-{ESO}-1}, journal = {Journal of Clinical Oncology}, year = {2011}, volume = {29}, number = {7}, pages = {917--924}, month = {mar}, doi = {10.1200/jco.2010.32.2537}, publisher = {American Society of Clinical Oncology ({ASCO})}, } @Article{Roddie2019, author = {Claire Roddie and Maeve O'Reilly and Juliana Dias Alves Pinto and Ketki Vispute and Mark Lowdell}, title = {Manufacturing chimeric antigen receptor T cells: issues and challenges}, journal = {Cytotherapy}, year = {2019}, month = {jan}, doi = {10.1016/j.jcyt.2018.11.009}, publisher = {Elsevier {BV}}, } @Article{Rosato2019, author = {Pamela C. Rosato and Sathi Wijeyesinghe and J. Michael Stolley and Christine E. Nelson and Rachel L. Davis and Luke S. Manlove and Christopher A. Pennell and Bruce R. Blazar and Clark C. Chen and Melissa A. Geller and Vaiva Vezys and David Masopust}, title = {Virus-specific memory T cells populate tumors and can be repurposed for tumor immunotherapy}, journal = {Nature Communications}, year = {2019}, volume = {10}, number = {1}, month = {feb}, doi = {10.1038/s41467-019-08534-1}, publisher = {Springer Nature}, } @Article{Rio2018, author = {Eduardo P{\'{e}}rez del R{\'{\i}}o and Marc Martinez Miguel and Jaume Veciana and Imma Ratera and Judith Guasch}, title = {Artificial 3D Culture Systems for T Cell Expansion}, journal = {{ACS} Omega}, year = {2018}, volume = {3}, number = {5}, pages = {5273--5280}, month = {may}, doi = {10.1021/acsomega.8b00521}, publisher = {American Chemical Society ({ACS})}, } @Article{Sart2011, author = {S{\'{e}}bastien Sart and Abdelmounaim Errachid and Yves-Jacques Schneider and Spiros N Agathos}, title = {Controlled expansion and differentiation of mesenchymal stem cells in a microcarrier based stirred bioreactor}, journal = {{BMC} Proceedings}, year = {2011}, volume = {5}, number = {S8}, month = {nov}, doi = {10.1186/1753-6561-5-s8-p55}, publisher = {Springer Nature}, } @Article{Schmoldt1975, author = {Schmoldt, A and Benthe, H F and Haberland, G}, title = {Digitoxin metabolism by rat liver microsomes.}, journal = {Biochemical pharmacology}, year = {1975}, volume = {24}, pages = {1639--1641}, month = sep, issn = {1873-2968}, chemicals = {Digitoxigenin, NADP, Digitoxin}, citation-subset = {IM}, completed = {1976-01-23}, country = {England}, issn-linking = {0006-2952}, issue = {17}, keywords = {Animals; Chromatography, Thin Layer; Digitoxigenin, metabolism; Digitoxin, metabolism; Hydroxylation; In Vitro Techniques; Male; Microsomes, Liver, metabolism; NADP, metabolism; Rats; Time Factors}, nlm-id = {0101032}, owner = {NLM}, pii = {0006-2952(75)90094-5}, pmid = {10}, pubmodel = {Print}, pubstatus = {ppublish}, revised = {2019-02-06}, } @Article{Sommermeyer2015, author = {D Sommermeyer and M Hudecek and P L Kosasih and T Gogishvili and D G Maloney and C J Turtle and S R Riddell}, title = {Chimeric antigen receptor-modified T cells derived from defined {CD}8+ and {CD}4+ subsets confer superior antitumor reactivity in vivo}, journal = {Leukemia}, year = {2015}, volume = {30}, number = {2}, pages = {492--500}, month = {sep}, doi = {10.1038/leu.2015.247}, publisher = {Springer Nature}, } @Article{Straetemans2018, author = {Trudy Straetemans and Guido J. J. Kierkels and Ruud Doorn and Koen Jansen and Sabine Heijhuurs and Joao M. dos Santos and Anna D. D. van Muyden and Henri Vie and B{\'{e}}atrice Clemenceau and Reinier Raymakers and Moniek de Witte and Zsolt Sebesty{\'{e}}n and Jürgen Kuball}, title = {{GMP}-Grade Manufacturing of T Cells Engineered to Express a Defined $\upgamma$$\updelta${TCR}}, journal = {Frontiers in Immunology}, year = {2018}, volume = {9}, month = {may}, doi = {10.3389/fimmu.2018.01062}, publisher = {Frontiers Media {SA}}, } @Article{Tumaini2013, author = {Tumaini, Barbara and Lee, Daniel W and Lin, Tasha and Castiello, Luciano and Stroncek, David F and Mackall, Crystal and Wayne, Alan and Sabatino, Marianna}, journal = {Cytotherapy}, title = {{Simplified process for the production of anti-CD19-CAR-engineered T cells.}}, year = {2013}, issn = {1477-2566}, month = {nov}, number = {11}, pages = {1406--15}, volume = {15}, abstract = {BACKGROUND AIMS: Adoptive immunotherapy with the use of chimeric antigen receptor (CAR)-engineered T cells specific for CD19 has shown promising results for the treatment of B-cell lymphomas and leukemia. This therapy involves the transduction of autologous T cells with a viral vector and the subsequent cell expansion. We describe a new, simplified method to produce anti-CD19-CAR T cells. METHODS: T cells were isolated from peripheral blood mononuclear cell (PBMC) with anti-CD3/anti-CD28 paramagnetic beads. After 2 days, the T cells were added to culture bags pre-treated with RetroNectin and loaded with the retroviral anti-CD19 CAR vector. The cells, beads and vector were incubated for 24 h, and a second transduction was then performed. No spinoculation was used. Cells were then expanded for an additional 9 days. RESULTS: The method was validated through the use of two PBMC products from a patient with B-cell chronic lymphoblastic leukemia and one PBMC product from a healthy subject. The two PBMC products from the patient with B-cell chronic lymphoblastic leukemia contained 11.4{\%} and 12.9{\%} T cells. The manufacturing process led to final products highly enriched in T cells with a mean CD3+ cell content of 98{\%}, a mean expansion of 10.6-fold and a mean transduction efficiency of 68{\%}. Similar results were obtained from the PBMCs of the first four patients with acute lymphoblastic leukemia treated at our institution. CONCLUSIONS: We developed a simplified, semi-closed system for the initial selection, activation, transduction and expansion of T cells with the use of anti-CD3/anti-CD28 beads and bags to produce autologous anti-CD19 CAR-transduced T cells to support an ongoing clinical trial.}, annote = {a manufacturing process for CD19 CAR T cells. It does not appear that they used a bioreactor}, doi = {10.1016/j.jcyt.2013.06.003}, groups = {[ndwar:]}, keywords = {.article, Antigens, CD19, CD19: immunology, CD28, CD28: immunology, CD3, CD3: immunology, CAR, Cell Engineering, Cell Engineering: methods, Cells, Cultured, Cytotoxicity, Immunologic, Immunologic: genetics, Immunologic: immunology, Humans, Immunotherapy, Adoptive, Leukemia, Lymphocytic, Chronic, B-Cell, B-Cell: immunology, Leukocytes, Mononuclear, Mononuclear: cytology, Lymphocyte Activation, Lymphocyte Activation: immunology, Receptors, Antigen, Antigen: genetics, T cell, T-Lymphocytes, T-Lymphocytes: immunology, Transduction, Genetic, biomanufacturing}, mendeley-tags = {.article,CAR,T cell,biomanufacturing}, pmid = {23992830}, } @Article{Turtle2016, author = {Cameron J. Turtle and Laïla-Aïcha Hanafi and Carolina Berger and Michael Hudecek and Barbara Pender and Emily Robinson and Reed Hawkins and Colette Chaney and Sindhu Cherian and Xueyan Chen and Lorinda Soma and Brent Wood and Daniel Li and Shelly Heimfeld and Stanley R. Riddell and David G. Maloney}, title = {Immunotherapy of non-Hodgkin's lymphoma with a defined ratio of {CD}8+ and {CD}4+ {CD}19-specific chimeric antigen receptor{\textendash}modified T cells}, journal = {Science Translational Medicine}, year = {2016}, volume = {8}, number = {355}, pages = {355ra116--355ra116}, month = {sep}, doi = {10.1126/scitranslmed.aaf8621}, publisher = {American Association for the Advancement of Science ({AAAS})}, } @Article{Walseng2017, author = {Even Walseng and Hakan Köksal and Ibrahim M. Sektioglu and Anne F{\aa}ne and Gjertrud Skorstad and Gunnar Kvalheim and Gustav Gaudernack and Else Marit Inderberg and S{\'{e}}bastien Wälchli}, title = {A {TCR}-based Chimeric Antigen Receptor}, journal = {Scientific Reports}, year = {2017}, volume = {7}, number = {1}, month = {sep}, doi = {10.1038/s41598-017-11126-y}, publisher = {Springer Nature}, } @Article{Wang2018, author = {Dongrui Wang and Brenda Aguilar and Renate Starr and Darya Alizadeh and Alfonso Brito and Aniee Sarkissian and Julie R. Ostberg and Stephen J. Forman and Christine E. Brown}, title = {Glioblastoma-targeted {CD}4+ {CAR} T cells mediate superior antitumor activity}, journal = {{JCI} Insight}, year = {2018}, volume = {3}, number = {10}, month = {may}, doi = {10.1172/jci.insight.99048}, publisher = {American Society for Clinical Investigation}, } @Article{Wang2016, author = {Xiuyan Wang and Isabelle Rivi{\`{e}}re}, title = {Clinical manufacturing of {CAR} T cells: foundation of a promising therapy}, journal = {Molecular Therapy - Oncolytics}, year = {2016}, volume = {3}, pages = {16015}, doi = {10.1038/mto.2016.15}, publisher = {Elsevier {BV}}, } @Article{van_der_Windt_2012, author = {Gerritje~J.W. van~der~Windt and Bart Everts and Chih-Hao Chang and Jonathan~D. Curtis and Tori~C. Freitas and Eyal Amiel and Edward~J. Pearce and Erika~L. Pearce}, title = {Mitochondrial Respiratory Capacity Is a Critical Regulator of {CD}8+ T Cell Memory Development}, journal = {Immunity}, year = {2012}, volume = {36}, number = {1}, pages = {68--78}, month = {jan}, doi = {10.1016/j.immuni.2011.12.007}, publisher = {Elsevier {BV}}, } @Article{Xu2014, author = {Xu, Yang and Zhang, Ming and Ramos, Carlos A and Durett, April and Liu, Enli and Dakhova, Olga and Liu, Hao and Creighton, Chad J and Gee, Adrian P and Heslop, Helen E and Rooney, Cliona M and Savoldo, Barbara and Dotti, Gianpietro}, journal = {Blood}, title = {Closely related T-memory stem cells correlate with in vivo expansion of CAR.CD19-T cells and are preserved by IL-7 and IL-15.}, year = {2014}, issn = {1528-0020}, month = jun, pages = {3750--3759}, volume = {123}, abstract = {Adoptive transfer of T lymphocytes expressing a CD19-specific chimeric antigen receptor (CAR.CD19) induces complete tumor regression in patients with lymphoid malignancies. Although in vivo persistence of CAR-T cells correlates with clinical responses, it remains unknown whether specific cell subsets within the CAR-T-cell product correlate with their subsequent in vivo expansion and persistence. We analyzed 14 patients with B-cell malignancies infused with autologous CAR.CD19-redirected T cells expanded ex vivo using IL-2, and found that their in vivo expansion only correlated with the frequency within the infused product of a CD8(+)CD45RA(+)CCR7(+) subset, whose phenotype is closest to "T-memory stem cells." Preclinical models showed that increasing the frequency of CD8(+)CD45RA(+)CCR7(+) CAR-T cells in the infused line by culturing the cells with IL-7 and IL-15 produced greater antitumor activity of CAR-T cells mediated by increased resistance to cell death, following repetitive encounters with the antigen, while preserving their migration to secondary lymphoid organs. This trial was registered at www.clinicaltrials.gov as NCT00586391 and NCT00709033.}, chemicals = {Antigens, CD19, Interleukin-15, Interleukin-7, Receptors, Antigen, Recombinant Fusion Proteins}, citation-subset = {AIM, IM}, completed = {2014-08-12}, country = {United States}, doi = {10.1182/blood-2014-01-552174}, issn-linking = {0006-4971}, issue = {24}, keywords = {Adoptive Transfer, methods; Adult Stem Cells, drug effects, metabolism, physiology, transplantation; Animals; Antigens, CD19, genetics, metabolism; Cell Proliferation, drug effects; Cells, Cultured; Genetic Therapy, methods; Humans; Immunologic Memory; Interleukin-15, pharmacology; Interleukin-7, pharmacology; Lymphocyte Activation, drug effects; Lymphoma, immunology, therapy; Mice; Mice, SCID; Mice, Transgenic; Receptors, Antigen, metabolism; Recombinant Fusion Proteins, metabolism; T-Lymphocytes, transplantation}, nlm-id = {7603509}, owner = {NLM}, pii = {blood-2014-01-552174}, pmc = {PMC4055922}, pmid = {24782509}, pubmodel = {Print-Electronic}, pubstatus = {ppublish}, revised = {2018-11-13}, } @Article{Yang2017, author = {Yinmeng Yang and M. Eric Kohler and Christopher D. Chien and Christopher T. Sauter and Elad Jacoby and Chunhua Yan and Ying Hu and Kelsey Wanhainen and Haiying Qin and Terry J. Fry}, title = {{TCR} engagement negatively affects {CD}8 but not {CD}4 {CAR} T cell expansion and leukemic clearance}, journal = {Science Translational Medicine}, year = {2017}, volume = {9}, number = {417}, pages = {eaag1209}, month = {nov}, doi = {10.1126/scitranslmed.aag1209}, publisher = {American Association for the Advancement of Science ({AAAS})}, } @Article{Zah2016, author = {Zah, Eugenia and Lin, Meng-Yin and Silva-Benedict, Anne and Jensen, Michael C and Chen, Yvonne Y}, journal = {Cancer immunology research}, title = {T Cells Expressing CD19/CD20 Bispecific Chimeric Antigen Receptors Prevent Antigen Escape by Malignant B Cells.}, year = {2016}, issn = {2326-6074}, month = jun, pages = {498--508}, volume = {4}, abstract = {The adoptive transfer of T cells expressing anti-CD19 chimeric antigen receptors (CARs) has shown remarkable curative potential against advanced B-cell malignancies, but multiple trials have also reported patient relapses due to the emergence of CD19-negative leukemic cells. Here, we report the design and optimization of single-chain, bispecific CARs that trigger robust cytotoxicity against target cells expressing either CD19 or CD20, two clinically validated targets for B-cell malignancies. We determined the structural parameters required for efficient dual-antigen recognition, and we demonstrate that optimized bispecific CARs can control both wild-type B-cell lymphoma and CD19(-) mutants with equal efficiency in vivo To our knowledge, this is the first bispecific CAR capable of preventing antigen escape by performing true OR-gate signal computation on a clinically relevant pair of tumor-associated antigens. The CD19-OR-CD20 CAR is fully compatible with existing T-cell manufacturing procedures and implementable by current clinical protocols. These results present an effective solution to the challenge of antigen escape in CD19 CAR T-cell therapy, and they highlight the utility of structure-based rational design in the development of receptors with higher-level complexity. Cancer Immunol Res; 4(6); 498-508. ©2016 AACR}, chemicals = {Antibodies, Bispecific, Antigens, CD19, Antigens, CD20, CD19 molecule, human, Cytokines, Receptors, Antigen, T-Cell, Recombinant Fusion Proteins}, citation-subset = {IM}, completed = {2017-01-17}, country = {United States}, doi = {10.1158/2326-6066.CIR-15-0231}, issn-linking = {2326-6066}, issue = {6}, keywords = {Animals; Antibodies, Bispecific, immunology; Antigens, CD19, CD20, immunology; CD8-Positive T-Lymphocytes, immunology; Cell Differentiation, immunology; Cytokines, biosynthesis; Cytotoxicity, Immunologic, immunology; Humans; Immunotherapy, Adoptive, methods; K562 Cells; Lymphoma, B-Cell, immunology, therapy; Mice, Inbred NOD; Mice, SCID; Receptors, Antigen, T-Cell, immunology; Recombinant Fusion Proteins, immunology; Tumor Cells, Cultured; Tumor Escape, immunology; Xenograft Model Antitumor Assays}, mid = {NIHMS781209}, nlm-id = {101614637}, owner = {NLM}, pii = {2326-6066.CIR-15-0231}, pmc = {PMC4933590}, pmid = {27059623}, pubmodel = {Print-Electronic}, pubstatus = {ppublish}, revised = {2018-11-13}, } @Article{Araki2009, author = {Koichi Araki and Alexandra P. 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Signal transduction mediated by the integrin family of cell adhesion receptors has been previously shown to modulate apoptosis in a number of different cell types; in T cells, integrin signaling is known to be important in cellular response to antigenic challenge by providing a co-stimulatory signal for TCR. In this study we demonstrate that signaling via the collagen receptor alpha2beta1 integrin specifically inhibits AICD by inhibiting Fas-L expression in activated Jurkat T cells. Engagement of the alpha2beta1 integrin with monoclonal antibodies or with type I collagen, a cognate ligand for alpha2beta1, reduced anti-CD3 and PMA/ionomycin-induced cell death by 30% and 40%, respectively, and the expression of Fas-L mRNA by 50%. Further studies indicated that the alpha2beta1-mediated inhibition of AICD and Fas-L expression required the focal adhesion kinase FAK, a known component in the integrin signaling pathways. These results suggest a role for the alpha2beta1 integrin in the control of homeostasis of immune response and T-cell development. (Blood. 2000;95:2044-2051)}, chemicals = {CD3 Complex, Cell Adhesion Molecules, FASLG protein, human, Fas Ligand Protein, Integrins, Ionophores, Membrane Glycoproteins, Protein Synthesis Inhibitors, RNA, Messenger, Receptors, Collagen, Ionomycin, Collagen, Cycloheximide, FAK-related nonkinase, Protein-Tyrosine Kinases, Focal Adhesion Kinase 1, Focal Adhesion Protein-Tyrosine Kinases, PTK2 protein, human, Tetradecanoylphorbol Acetate}, citation-subset = {AIM, IM}, completed = {2000-04-07}, country = {United States}, issn-linking = {0006-4971}, issue = {6}, keywords = {Apoptosis; CD3 Complex, metabolism; Cell Adhesion Molecules, metabolism; Cell Death; Collagen, metabolism; Cycloheximide, pharmacology; DNA Fragmentation; Fas Ligand Protein; Flow Cytometry; Focal Adhesion Kinase 1; Focal Adhesion Protein-Tyrosine Kinases; Humans; Integrins, metabolism; Ionomycin, pharmacology; Ionophores, pharmacology; Jurkat Cells; Membrane Glycoproteins, metabolism; Plasmids; Protein Synthesis Inhibitors, pharmacology; Protein-Tyrosine Kinases, metabolism; RNA, Messenger, metabolism; Receptors, Collagen; Signal Transduction; T-Lymphocytes, metabolism, pathology; Tetradecanoylphorbol Acetate, pharmacology; Transfection}, nlm-id = {7603509}, owner = {NLM}, pii = {S0006-4971(20)66967-1}, pmid = {10706873}, pubmodel = {Print}, pubstate = {ppublish}, revised = {2021-02-16}, } @Article{Hemler1990, author = {Hemler, M. 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Goldstein and Holbrook E. Kohrt and Roch Houot and Bindu Varghese and Jack T. Lin and Erica Swanson and Ronald Levy}, journal = {Cancer Research}, title = {Adoptive Cell Therapy for Lymphoma with {CD}4 T Cells Depleted of {CD}137-Expressing Regulatory T Cells}, year = {2012}, month = {jan}, number = {5}, pages = {1239--1247}, volume = {72}, doi = {10.1158/0008-5472.can-11-3375}, publisher = {American Association for Cancer Research ({AACR})}, } @Article{Drela2004, author = {Nadzieja Drela and Ahmad Jalili and Rafal Kaminski and Katarzyna Kozar and Marek Jak�bisiak and Witold Lasek and Grzegorz Basak and Tomasz Switaj and Anna B. Jakubowska and Piotr J. Wysocki and Andrzej Mackiewicz}, journal = {Cancer Immunology, Immunotherapy}, title = {Complete tumour regressions induced by vaccination with {IL}-12 gene-transduced tumour cells in combination with {IL}-15 in a melanoma model in mice}, year = {2004}, month = {apr}, number = {4}, pages = {363--372}, volume = {53}, doi = {10.1007/s00262-003-0449-9}, publisher = {Springer Science and Business Media {LLC}}, } @Article{Rankin2003, author = {Rankin, Erinn B. and Yu, Duonan and Jiang, Jiu and Shen, Hao and Pearce, Edward J. and Goldschmidt, Michael H. and Levy, David E. and Golovkina, Tatyana V. and Hunter, Christopher A. and Thomas-Tikhonenko, Andrei}, journal = {Cancer biology and therapy}, title = {An essential role of {Th1} responses and interferon gamma in infection-mediated suppression of neoplastic growth.}, year = {2003}, issn = {1538-4047}, pages = {687--693}, volume = {2}, abstract = {We had previously demonstrated that in mice acute toxoplasmosis leads to systemic inhibition of angiogenesis and, consequently, strong suppression of neoplastic growth. Here we investigated the role of Th1 cytokines, in particular interferon gamma (IFN-gamma), in this phenomenon. Besides toxoplasma, neoplastic growth was readily blocked during acute infection with other Th1 response-inducing pathogens such as Listeria monocytogenes and lymphocytic choriomeningitis virus (LCMV). In contrast, chronic infection with LCMV (when Th1 responses were strongly suppressed) and acute infection with Schistosoma mansoni (when Th2 responses predominated) afforded no anti-tumor protection. To corroborate the involvement of Th1 cytokines in infection-mediated suppression of neoplastic growth, we utilized mice deficient in interleukin-10 (IL10), a suppressor of Th1 responses. When challenged with B16 cells concomitantly with toxoplasma infection, both IL10-null and wild type mice exhibited resistance to neoplastic growth. However, tumors borne by IL10-null animals were even smaller than those borne by their wild type counterparts. This enhanced resistance correlated with dramatically elevated levels of circulating IFN-gamma, a principal Th1 cytokine. Furthermore, while interleukin-12 and tumor necrosis factor a were dispensable for tumor suppression, in animals deficient in IFN-gamma production or signaling, tumor growth and neovascularization were markedly enhanced. Interestingly, the enhancement was also apparent in uninfected animals suggesting that IFN-gamma and its anti-angiogenic effects underlie both infection-dependent and -independent tumor surveillance.}, chemicals = {Culture Media, Conditioned, Cytokines, Drug Combinations, Laminin, Proteoglycans, Vascular Endothelial Growth Factor A, matrigel, Interleukin-10, Interferon-gamma, Collagen}, citation-subset = {IM}, completed = {2004-09-13}, country = {United States}, issn-linking = {1538-4047}, issue = {6}, keywords = {Acute Disease; Animals; Cell Line, Tumor; Cell Transplantation; Clone Cells; Collagen, metabolism; Culture Media, Conditioned, analysis; Cytokines, immunology; Drug Combinations; Infections, blood, immunology; Interferon-gamma, analysis, immunology; Interleukin-10, deficiency; Laminin, metabolism; Listeria monocytogenes, pathogenicity; Lymphocytic choriomeningitis virus, pathogenicity; Melanoma, Experimental, blood, immunology, pathology; Mice; Mice, Inbred C57BL; Mice, Knockout; Models, Biological; Neovascularization, Pathologic; Proteoglycans, metabolism; Th1 Cells, immunology; Time Factors; Toxoplasma, pathogenicity; Toxoplasmosis; Vascular Endothelial Growth Factor A, analysis, genetics, metabolism}, nlm-id = {101137842}, owner = {NLM}, pii = {557}, pmid = {14688478}, pubmodel = {Print}, pubstate = {ppublish}, revised = {2020-09-30}, } @Article{Luheshi2013, author = {Nadia Luheshi and Gareth Davies and Edmund Poon and Kimberley Wiggins and Matthew McCourt and James Legg}, journal = {European Journal of Immunology}, title = {Th1 cytokines are more effective than Th2 cytokines at licensing anti-tumour functions in {CD}40-activated human macrophages in vitro}, year = {2013}, month = {oct}, number = {1}, pages = {162--172}, volume = {44}, doi = {10.1002/eji.201343351}, publisher = {Wiley}, } @Article{Grotz2015, author = {Travis E Grotz and James W Jakub and Aaron S Mansfield and Rachel Goldenstein and Elizabeth Ann L Enninga and Wendy K Nevala and Alexey A Leontovich and Svetomir N Markovic}, journal = {{OncoImmunology}}, title = {Evidence of Th2 polarization of the sentinel lymph node ({SLN}) in melanoma}, year = {2015}, month = {jun}, number = {8}, pages = {e1026504}, volume = {4}, doi = {10.1080/2162402x.2015.1026504}, publisher = {Informa {UK} Limited}, } @Article{Ando2019, author = {Makoto Ando and Minako Ito and Tanakorn Srirat and Taisuke Kondo and Akihiko Yoshimura}, journal = {Immunological Medicine}, title = {Memory T cell, exhaustion, and tumor immunity}, year = {2019}, month = {dec}, number = {1}, pages = {1--9}, volume = {43}, doi = {10.1080/25785826.2019.1698261}, publisher = {Informa {UK} Limited}, } @Article{Wherry2015, author = {E. John Wherry and Makoto Kurachi}, journal = {Nature Reviews Immunology}, title = {Molecular and cellular insights into T cell exhaustion}, year = {2015}, month = {jul}, number = {8}, pages = {486--499}, volume = {15}, doi = {10.1038/nri3862}, publisher = {Springer Science and Business Media {LLC}}, } @Article{Zheng2017, author = {Chunhong Zheng and Liangtao Zheng and Jae-Kwang Yoo and Huahu Guo and Yuanyuan Zhang and Xinyi Guo and Boxi Kang and Ruozhen Hu and Julie Y. Huang and Qiming Zhang and Zhouzerui Liu and Minghui Dong and Xueda Hu and Wenjun Ouyang and Jirun Peng and Zemin Zhang}, journal = {Cell}, title = {Landscape of Infiltrating T Cells in Liver Cancer Revealed by Single-Cell Sequencing}, year = {2017}, month = {jun}, number = {7}, pages = {1342--1356.e16}, volume = {169}, doi = {10.1016/j.cell.2017.05.035}, publisher = {Elsevier {BV}}, } @Comment{jabref-meta: databaseType:bibtex;} @Comment{jabref-meta: grouping: 0 AllEntriesGroup:; 1 StaticGroup:Markings\;2\;1\;\;\;\;; 2 StaticGroup:[ndwar:]\;2\;1\;\;\;\;; 2 StaticGroup:ndwar:6\;2\;1\;\;\;\;; }