From 8d82f1424dff8b5064080bcd3a3b8a5498ba4925 Mon Sep 17 00:00:00 2001
From: ndwarshuis <ndwar@yavin4.ch>
Date: Tue, 27 Jul 2021 18:27:13 -0400
Subject: [PATCH] ADD results for mouse 1 QC

---
 tex/thesis.tex | 31 +++++++++++++++++++++----------
 1 file changed, 21 insertions(+), 10 deletions(-)

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}