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ADD results for mouse 1 QC

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Nathan Dwarshuis 2021-07-27 18:27:13 -04:00
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@ -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 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 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} 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 Nalm-6 tumor cells expression firefly luciferase\cite{Fraietta2018}. After
cell growth (\cref{fig:mouse_dosing_overview}), we intravenously injected saline \SI{7}{\day} of tumor cell growth (\cref{fig:mouse_dosing_overview}), we
or three doses (high, medium, and low) of \gls{dms} T cells from either bead or intravenously injected saline or three doses (high, medium, and low) of
DMS cultures expanded for \SI{14}{\day}. We quantified total \gls{dms} \gls{dms} T cells from either bead or DMS cultures expanded for \SI{14}{\day}.
expressing T cell percentage for bead and \gls{dms} groups using the \gls{ptnl} We quantified total \gls{dms} expressing T cell percentage for bead and
assay (\cref{tab:mouse_dosing_results}). \gls{dms} groups using the \gls{ptnl} assay (\cref{tab:mouse_dosing_results}).
% RESULT explain the qc results 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
% FIGURE add the full survival curve as (sup figure 7) 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 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 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 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 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 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{} \subsection{DMS-expanded T cells show greater anti-tumor activity \invivo{}
compared to beads} compared to beads}