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ADD discussion to mouse 2

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Nathan Dwarshuis 2021-07-28 16:12:15 -04:00
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@ -2393,8 +2393,10 @@ We performed the same experiments as described in
\cref{fig:mouse_dosing_overview} with the modification that T cells were only \cref{fig:mouse_dosing_overview} with the modification that T cells were only
grown and harvested after \SI{6}{\day}, \SI{10}{\day}, or \SI{14}{\day} of grown and harvested after \SI{6}{\day}, \SI{10}{\day}, or \SI{14}{\day} of
expansion (\cref{fig:mouse_timecourse_overview}). T cells were frozen after expansion (\cref{fig:mouse_timecourse_overview}). T cells were frozen after
harvest, and all timepoints were thawed at the same time prior to injection. All harvest, and all timepoints were thawed at the same time prior to injection. The
other characteristics of the experiment were the same. dose of T cells injected was \num{1.25e6} cells per mouse (the same as the high
dose in the first experiment). All other characteristics of the experiment were
the same.
\begin{figure*}[ht!] \begin{figure*}[ht!]
\begingroup \begingroup
@ -2486,6 +2488,9 @@ other groups in regard to the final tumor burden.
\section{discussion} \section{discussion}
% TABLE make a summary table showing the results from both experiments; this is
% tough to explain.
When we tested bead and DMS expanded \gls{car} T cells, we also found that the When we tested bead and DMS expanded \gls{car} T cells, we also found that the
\gls{dms} expanded CAR-T cells outperformed bead groups in prolonging survival \gls{dms} expanded CAR-T cells outperformed bead groups in prolonging survival
of Nalm-6 tumor challenged (intravenously injected) \gls{nsg} mice. DMS expanded of Nalm-6 tumor challenged (intravenously injected) \gls{nsg} mice. DMS expanded
@ -2500,7 +2505,21 @@ results suggest that the higher proportion of memory T cells in DMS groups
efficiently kill tumor cells as recently reported in efficiently kill tumor cells as recently reported in
literature\cite{Fraietta2018, Sommermeyer2015}. literature\cite{Fraietta2018, Sommermeyer2015}.
% DISCUSSION 2nd mouse model % TODO try and find literature explaining what the ideal ratio is
When testing \gls{car} T cells at earlier timepoints relative to day 14 as used
in the first \invivo{} experiment, we noted that none of the \gls{car}
treatments seemed to work as well as they did in the first experiment. However,
at day 14, we should note that the number of \gls{car} T cells injected in the
second experiment was lower than the lowest dose in the first for both bead and
\gls{dms} (\cref{fig:mouse_timecourse_qc_car,tab:mouse_dosing_results}). While
the \ptmemp{} generally increases with earlier timepoints in the second
experiment, the first experiment suggests that \ptmemp{} may not be the primary
driver in this particular model
(\cref{fig:mouse_timecourse_qc_mem,fig:mouse_dosing_qc_mem}). As with the first
experiment, the \pthp{} seems to be higher overall in the \gls{dms} group than
the bead group (\cref{fig:mouse_dosing_qc_cd4,fig:mouse_timecourse_qc_cd4}), and
this may explain the modest advantage that the \gls{dms} T cells seemed to have
in the second experiment in slowing the progression of tumor burden.
\chapter{conclusions and future work}\label{conclusions} \chapter{conclusions and future work}\label{conclusions}
\section{conclusions} \section{conclusions}