diff --git a/tex/thesis.tex b/tex/thesis.tex index 6726fdf..c027472 100644 --- a/tex/thesis.tex +++ b/tex/thesis.tex @@ -2162,16 +2162,21 @@ 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}). +Nalm-6 tumor cells expression firefly luciferase\cite{Fraietta2018}. 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) +Before injecting the T cells into the mice, we quantified their phenotype and +growth. We observed that for this expansion, the bead and \gls{dms} T cells +produced similar numbers of \ptmem{} T cells, and the beads even had a higher +fraction of CD45RA, which is present on lower-differentiated naive and +stem-memory T cells (\cref{fig:mouse_dosing_qc_mem}). However, the \pthp{} of +the final product was higher in \gls{dms} (\cref{fig:mouse_dosing_qc_cd4}). The +\gls{dms} T cells also expanded more robustly than the beads +(\cref{fig:mouse_dosing_qc_growth}). 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 @@ -2201,7 +2206,13 @@ 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. +cells are effective at lower doses. Given the quality control data of the T +cells prior to injecting into the mice, it seems that this advantage is either +due to the higher \pthp{} or the overall fitness of the T cells given the higher +expansion in the case of \gls{dms} +(\cref{fig:mouse_dosing_qc_cd4,fig:mouse_dosing_qc_growth}). It was likely not +due to the memory phenotype given that it was actually slightly higher in the +case of beads (\cref{fig:mouse_dosing_qc_mem}). \subsection{DMS-expanded T cells show greater anti-tumor activity \invivo{} compared to beads}