ADD results for mouse model 1
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@Article{Gattinoni2012,
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author = {Gattinoni, Luca and Klebanoff, Christopher A and Restifo, Nicholas P},
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title = {{Paths to stemness: building the ultimate antitumour T cell.}},
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journal = {Nature reviews. Cancer},
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title = {{Paths to stemness: building the ultimate antitumour T cell.}},
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year = {2012},
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volume = {12},
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issn = {1474-1768},
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month = {oct},
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number = {10},
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pages = {671--84},
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month = {oct},
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issn = {1474-1768},
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volume = {12},
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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.},
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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},
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doi = {10.1038/nrc3322},
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@ -111,18 +111,18 @@
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@Article{Kalos2011,
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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},
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title = {{T cells with chimeric antigen receptors have potent antitumor effects and can establish memory in patients with advanced leukemia.}},
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journal = {Science translational medicine},
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title = {{T cells with chimeric antigen receptors have potent antitumor effects and can establish memory in patients with advanced leukemia.}},
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year = {2011},
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volume = {3},
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issn = {1946-6242},
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month = {aug},
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number = {95},
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pages = {95ra73},
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month = {aug},
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issn = {1946-6242},
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__markedentry = {[ndwar:]},
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volume = {3},
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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.},
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annote = {the paper from Levine/June that includes the CD107a cytotox assay},
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doi = {10.1126/scitranslmed.3002842},
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groups = {[ndwar:]},
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isbn = {1946-6242 (Electronic) 1946-6234 (Linking)},
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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},
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mendeley-tags = {.article,CAR,T cell},
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@ -131,15 +131,15 @@
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@Article{Bashour2015,
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author = {Bashour, Keenan T and Larson, Ryan P and Graef, Patricia and Stemberger, Christian and Lothar, Germeroth and Odegard, Valerie and Ramsborg, Christopher G},
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title = {Functional Characterization of a T Cell Stimulation Reagent for the Production of Therapeutic Chimeric Antigen Receptor T Cells},
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journal = {Blood},
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title = {Functional Characterization of a T Cell Stimulation Reagent for the Production of Therapeutic Chimeric Antigen Receptor T Cells},
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year = {2015},
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volume = {126},
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issn = {0006-4971},
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number = {23},
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pages = {1901--1901},
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issn = {0006-4971},
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__markedentry = {[ndwar:6]},
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volume = {126},
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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.},
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groups = {ndwar:6},
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publisher = {American Society of Hematology},
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}
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@ -247,16 +247,16 @@
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@Article{Buck2016,
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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.},
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title = {{Mitochondrial Dynamics Controls T Cell Fate through Metabolic Programming}},
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journal = {Cell},
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title = {{Mitochondrial Dynamics Controls T Cell Fate through Metabolic Programming}},
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year = {2016},
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volume = {166},
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pages = {114},
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month = {jun},
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issn = {00928674},
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__markedentry = {[ndwar:]},
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month = {jun},
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pages = {114},
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volume = {166},
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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.},
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doi = {10.1016/j.cell.2016.05.035},
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groups = {[ndwar:]},
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keywords = {.article, T cell, metabolism},
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mendeley-tags = {.article,T cell,metabolism},
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}
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@ -315,12 +315,12 @@
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@Article{Delalat2017,
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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.},
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title = {{3D printed lattices as an activation and expansion platform for T cell therapy}},
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journal = {Biomaterials},
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title = {{3D printed lattices as an activation and expansion platform for T cell therapy}},
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year = {2017},
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volume = {140},
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pages = {58--68},
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issn = {18785905},
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pages = {58--68},
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volume = {140},
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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.},
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doi = {10.1016/j.biomaterials.2017.05.009},
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keywords = {.article, 3D lattice, Cell therapy manufacturing, Immunotherapy, Melt electrospin writing, Plasma polymer functionalization, T cell, biomanufacturing},
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@ -381,17 +381,17 @@
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@Article{Gerdemann2011,
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author = {Gerdemann, Ulrike and Vera, Juan F and Rooney, Cliona M and Leen, Ann M},
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title = {{Generation of multivirus-specific T cells to prevent/treat viral infections after allogeneic hematopoietic stem cell transplant.}},
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journal = {Journal of visualized experiments : JoVE},
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title = {{Generation of multivirus-specific T cells to prevent/treat viral infections after allogeneic hematopoietic stem cell transplant.}},
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year = {2011},
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number = {51},
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month = {jan},
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issn = {1940-087X},
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__markedentry = {[ndwar:]},
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month = {jan},
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number = {51},
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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.},
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annote = {a protocol that demonstrated the G-Rex used to make virus-specific T cells},
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doi = {10.3791/2736},
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keywords = {.protocol,Antigen-Presenting Cells,Antigen-Presenting Cells: immunology,Dendritic Cells,Dendritic Cells: immunology,Epitopes, T-Lymphocyte,Epitopes, T-Lymphocyte: immunology,Hematopoietic Stem Cell Transplantation,Hematopoietic Stem Cell Transplantation: adverse e,Hematopoietic Stem Cell Transplantation: methods,Humans,Immunotherapy, Adoptive,Immunotherapy, Adoptive: methods,Lymphocyte Activation,T cell,T-Lymphocytes, Cytotoxic,T-Lymphocytes, Cytotoxic: immunology,Virus Diseases,Virus Diseases: etiology,Virus Diseases: immunology,Virus Diseases: prevention {\&} control,Virus Diseases: therapy,biomanufacturing},
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groups = {[ndwar:]},
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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},
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mendeley-tags = {.protocol,T cell,biomanufacturing},
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pmid = {21654628},
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}
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@ -456,13 +456,13 @@
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@Article{Hromas1997,
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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},
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title = {Cloning and characterization of exodus, a novel beta-chemokine.},
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journal = {Blood},
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title = {Cloning and characterization of exodus, a novel beta-chemokine.},
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year = {1997},
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volume = {89},
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pages = {3315--3322},
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month = may,
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issn = {0006-4971},
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month = may,
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pages = {3315--3322},
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volume = {89},
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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.},
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chemicals = {CCL20 protein, human, CCR6 protein, human, Chemokine CCL20, Chemokines, Chemokines, CC, DNA, Complementary, Macrophage Inflammatory Proteins, Receptors, CCR6, Receptors, Chemokine, Recombinant Proteins},
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citation-subset = {AIM, IM, X},
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@ -470,7 +470,7 @@
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country = {United States},
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issn-linking = {0006-4971},
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issue = {9},
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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, biosynthesis, pharmacology; Sequence Homology, Amino Acid; Transcription, Genetic; Tumor Cells, Cultured},
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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},
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nlm-id = {7603509},
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owner = {NLM},
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pmid = {9129037},
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@Article{Jin2012,
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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},
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title = {{Simplified method of the growth of human tumor infiltrating lymphocytes in gas-permeable flasks to numbers needed for patient treatment.}},
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journal = {Journal of immunotherapy (Hagerstown, Md. : 1997)},
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title = {{Simplified method of the growth of human tumor infiltrating lymphocytes in gas-permeable flasks to numbers needed for patient treatment.}},
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year = {2012},
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volume = {35},
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issn = {1537-4513},
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month = {apr},
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number = {3},
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pages = {283--92},
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month = {apr},
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issn = {1537-4513},
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__markedentry = {[ndwar:]},
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volume = {35},
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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.},
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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},
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doi = {10.1097/CJI.0b013e31824e801f},
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keywords = {.article,Humans,Immunotherapy, Adoptive,Lymphocytes, Tumor-Infiltrating,Lymphocytes, Tumor-Infiltrating: cytology,Primary Cell Culture,Primary Cell Culture: instrumentation,Primary Cell Culture: methods,Primary Cell Culture: standards,T cell,TIL,biomanufacturing},
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groups = {[ndwar:]},
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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},
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mendeley-tags = {.article,T cell,TIL,biomanufacturing},
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pmid = {22421946},
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}
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@Article{Lambert2017,
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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.},
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title = {{Improving T Cell Expansion with a Soft Touch.}},
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journal = {Nano letters},
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title = {{Improving T Cell Expansion with a Soft Touch.}},
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year = {2017},
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volume = {17},
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issn = {1530-6992},
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month = {feb},
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number = {2},
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pages = {821--826},
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month = {feb},
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issn = {1530-6992},
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volume = {17},
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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.},
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doi = {10.1021/acs.nanolett.6b04071},
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keywords = {.article, T cell, immunotherapy, mechanobiology, nanoscale rigidity},
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@ -555,18 +555,18 @@
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@Article{Lamers2014,
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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},
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title = {{T cell receptor-engineered T cells to treat solid tumors: T cell processing toward optimal T cell fitness.}},
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journal = {Human gene therapy methods},
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title = {{T cell receptor-engineered T cells to treat solid tumors: T cell processing toward optimal T cell fitness.}},
|
||||
year = {2014},
|
||||
volume = {25},
|
||||
issn = {1946-6544},
|
||||
month = {dec},
|
||||
number = {6},
|
||||
pages = {345--57},
|
||||
month = {dec},
|
||||
issn = {1946-6544},
|
||||
__markedentry = {[ndwar:]},
|
||||
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},
|
||||
|
|
@ -574,14 +574,14 @@
|
|||
|
||||
@Article{Matic2013,
|
||||
author = {Matic, Jovana and Deeg, Janosch and Scheffold, Alexander and Goldstein, Itamar and Spatz, Joachim P.},
|
||||
title = {{Fine tuning and efficient T cell activation with stimulatory aCD3 nanoarrays.}},
|
||||
journal = {Nano letters},
|
||||
title = {{Fine tuning and efficient T cell activation with stimulatory aCD3 nanoarrays.}},
|
||||
year = {2013},
|
||||
volume = {13},
|
||||
issn = {1530-6992},
|
||||
month = {nov},
|
||||
number = {11},
|
||||
pages = {5090--7},
|
||||
month = {nov},
|
||||
issn = {1530-6992},
|
||||
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},
|
||||
|
|
@ -764,15 +764,14 @@
|
|||
|
||||
@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},
|
||||
title = {{Simplified process for the production of anti-CD19-CAR-engineered T cells.}},
|
||||
journal = {Cytotherapy},
|
||||
title = {{Simplified process for the production of anti-CD19-CAR-engineered T cells.}},
|
||||
year = {2013},
|
||||
volume = {15},
|
||||
issn = {1477-2566},
|
||||
month = {nov},
|
||||
number = {11},
|
||||
pages = {1406--15},
|
||||
month = {nov},
|
||||
issn = {1477-2566},
|
||||
__markedentry = {[ndwar:]},
|
||||
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.
|
||||
|
|
@ -782,7 +781,8 @@ RESULTS: The method was validated through the use of two PBMC products from a pa
|
|||
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},
|
||||
keywords = {.article,Antigens, CD19,Antigens, CD19: immunology,Antigens, CD28,Antigens, CD28: immunology,Antigens, CD3,Antigens, CD3: immunology,CAR,Cell Engineering,Cell Engineering: methods,Cells, Cultured,Cytotoxicity, Immunologic,Cytotoxicity, Immunologic: genetics,Cytotoxicity, Immunologic: immunology,Humans,Immunotherapy, Adoptive,Leukemia, Lymphocytic, Chronic, B-Cell,Leukemia, Lymphocytic, Chronic, B-Cell: immunology,Leukocytes, Mononuclear,Leukocytes, Mononuclear: cytology,Lymphocyte Activation,Lymphocyte Activation: immunology,Receptors, Antigen,Receptors, Antigen: genetics,T cell,T-Lymphocytes,T-Lymphocytes: immunology,Transduction, Genetic,biomanufacturing},
|
||||
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},
|
||||
}
|
||||
|
|
@ -850,14 +850,14 @@ CONCLUSIONS: We developed a simplified, semi-closed system for the initial selec
|
|||
|
||||
@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},
|
||||
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.},
|
||||
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},
|
||||
volume = {123},
|
||||
pages = {3750--3759},
|
||||
month = jun,
|
||||
issn = {1528-0020},
|
||||
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. },
|
||||
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},
|
||||
|
|
@ -865,7 +865,7 @@ CONCLUSIONS: We developed a simplified, semi-closed system for the initial selec
|
|||
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, genetics, immunology, therapy; Mice; Mice, SCID; Mice, Transgenic; Receptors, Antigen, genetics, metabolism; Recombinant Fusion Proteins, genetics, metabolism; T-Lymphocytes, drug effects, metabolism, physiology, transplantation},
|
||||
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},
|
||||
|
|
@ -891,13 +891,13 @@ CONCLUSIONS: We developed a simplified, semi-closed system for the initial selec
|
|||
|
||||
@Article{Zah2016,
|
||||
author = {Zah, Eugenia and Lin, Meng-Yin and Silva-Benedict, Anne and Jensen, Michael C and Chen, Yvonne Y},
|
||||
title = {T Cells Expressing CD19/CD20 Bispecific Chimeric Antigen Receptors Prevent Antigen Escape by Malignant B Cells.},
|
||||
journal = {Cancer immunology research},
|
||||
title = {T Cells Expressing CD19/CD20 Bispecific Chimeric Antigen Receptors Prevent Antigen Escape by Malignant B Cells.},
|
||||
year = {2016},
|
||||
volume = {4},
|
||||
pages = {498--508},
|
||||
month = jun,
|
||||
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},
|
||||
|
|
@ -906,7 +906,7 @@ CONCLUSIONS: We developed a simplified, semi-closed system for the initial selec
|
|||
doi = {10.1158/2326-6066.CIR-15-0231},
|
||||
issn-linking = {2326-6066},
|
||||
issue = {6},
|
||||
keywords = {Animals; Antibodies, Bispecific, immunology; Antigens, CD19, immunology; Antigens, 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},
|
||||
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},
|
||||
|
|
@ -1153,4 +1153,25 @@ CONCLUSIONS: We developed a simplified, semi-closed system for the initial selec
|
|||
publisher = {Wiley},
|
||||
}
|
||||
|
||||
@Article{Ali2012,
|
||||
author = {Niwa Ali and Barry Flutter and Robert Sanchez Rodriguez and Ehsan Sharif-Paghaleh and Linda D. Barber and Giovanna Lombardi and Frank O. Nestle},
|
||||
journal = {{PLoS} {ONE}},
|
||||
title = {Xenogeneic Graft-versus-Host-Disease in {NOD}-scid {IL}-2R$\upgamma$null Mice Display a T-Effector Memory Phenotype},
|
||||
year = {2012},
|
||||
month = {aug},
|
||||
number = {8},
|
||||
pages = {e44219},
|
||||
volume = {7},
|
||||
doi = {10.1371/journal.pone.0044219},
|
||||
editor = {Cheryl A. Stoddart},
|
||||
publisher = {Public Library of Science ({PLoS})},
|
||||
}
|
||||
|
||||
@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\;\;\;\;;
|
||||
}
|
||||
|
|
|
|||
|
|
@ -94,6 +94,7 @@
|
|||
\newacronym{cas37}{Cas3/7}{Caspase-3/7}
|
||||
\newacronym{bcl2}{BCL-2}{B cell lymphoma 2}
|
||||
\newacronym{tmb}{TMB}{3,3',5,5'-Tetramethylbenzidine}
|
||||
\newacronym{gvhd}{GVHD}{graft-vs-host disease}
|
||||
|
||||
%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%
|
||||
% SI units for uber nerds
|
||||
|
|
@ -1893,9 +1894,9 @@ provide these benefits.
|
|||
|
||||
\subsection{CD19-CAR T cell generation}
|
||||
|
||||
% TODO describe how T cells were grown for this aim
|
||||
% METHOD describe how T cells were grown for this aim
|
||||
|
||||
% TODO describe how the luciferase cells were generated (eg the kwong lab)
|
||||
% METHOD describe how the luciferase cells were generated (eg the kwong lab)
|
||||
|
||||
\subsection{\invivo{} therapeutic efficacy in NSG mice model}
|
||||
|
||||
|
|
@ -1927,6 +1928,52 @@ between survival groups.
|
|||
|
||||
\section{results}
|
||||
|
||||
We asked if the higher memory/naive phenotype and more balanced CD4/CD8 ratio of
|
||||
our \gls{dms}-expanded CAR T cells would lead to better anti-tumor potency in
|
||||
vivo compared to bead-expanded CAR T cells. We also asked if this superior
|
||||
anti-tumor potency would hold true at lower doses of CAR expressing T cells in
|
||||
the DMS group vs the bead group. To test this, we used a human xenograft model
|
||||
of B cell \gls{all} by intravenously injecting \gls{nsg} mice with \num{1e6}
|
||||
Nalm-6 tumor cells expression firefly luciferase20. After \SI{7}{\day} of tumor
|
||||
cell growth (\cref{fig:mouse_dosing_overview}), we intravenously injected saline
|
||||
or three doses (high, medium, and low) of \gls{dms} T cells from either bead or
|
||||
DMS cultures expanded for \SI{14}{\day}. We quantified total \gls{dms}
|
||||
expressing T cell percentage for bead and \gls{dms} groups using the \gls{ptnl}
|
||||
assay (\cref{tab:mouse_dosing_results}).
|
||||
|
||||
% RESULT explain the qc results
|
||||
|
||||
% FIGURE add the full survival curve as (sup figure 7)
|
||||
|
||||
In the Nalm-6/\gls{nsg} xenograft model, we observed lower tumor burden and
|
||||
significantly longer survival of bead and \gls{dms}-treated mice at all doses
|
||||
compared to the saline groups (\cref{fig:mouse_dosing_ivis}). Importantly, at
|
||||
each dose we observed that the \gls{dms}-treated mice had much lower tumor
|
||||
burden and significantly higher survival than their bead-treated counterparts
|
||||
(\cref{fig:mouse_dosing_ivis_survival}). When factoring the percentage T cells
|
||||
in each dose that expressed the \gls{car}, we note that survival of the low
|
||||
\gls{dms} dose (which had similar total \gls{car} T cells compared to the bead
|
||||
medium dose and less than the bead high dose) is significantly higher than that
|
||||
of both the bead medium dose and the bead high dose
|
||||
(\cref{fig:mouse_dosing_ivis_survival_comp}). Overall, the Kaplan-Meier survival
|
||||
of Nalm-6 tumor bearing \gls{nsg} mice shown in the
|
||||
\cref{fig:mouse_dosing_ivis_survival} was up to day 40 as reported
|
||||
elsewhere\cite{Fraietta2018}. However, we also included a Kaplan-Meier figure up
|
||||
to day 46 (Supplemental Figure 7) where most of the mice euthanized from day 40
|
||||
through day 46 from \gls{dms} groups showed no or very small fragment of spleen
|
||||
which was due to \gls{gvhd} responses. Similar \gls{gvhd} responses were
|
||||
reported earlier in \gls{nsg} mice where the mice injected with human \gls{pbmc}
|
||||
exhibited acute \gls{gvhd} between \SIrange{40}{50}{\day} post intravenous
|
||||
injection\cite{Ali2012}. Notably, both survival analyses (up to day 40 in
|
||||
\cref{fig:mouse_dosing_ivis_survival} and up to day 46 in Supplemental Figure 7)
|
||||
confirmed that \gls{dms}-expanded groups outperformed bead-expanded groups in
|
||||
terms of prolonging survival of Nalm-6 tumor challenged \gls{nsg} mice.
|
||||
|
||||
Together, these data suggested that \glspl{dms} produce T cells that are not
|
||||
only more potent that bead-expanded T cells (even when accounting for
|
||||
differences in \gls{car} expression) but also showed that \gls{dms} expanded T
|
||||
cells are effective at lower doses.
|
||||
|
||||
\subsection{DMS-expanded T cells show greater anti-tumor activity \invivo{}
|
||||
compared to beads}
|
||||
|
||||
|
|
|
|||
Loading…
Reference in New Issue