ADD introductions to all aims

This commit is contained in:
Nathan Dwarshuis 2021-07-31 18:19:31 -04:00
parent b7b500bf28
commit f6fc38aa79
1 changed files with 40 additions and 0 deletions

View File

@ -2024,6 +2024,22 @@ likely serve as a drop-in substitution to provide these benefits.
\chapter{aim 2a}\label{aim2a}
\section{introduction}
The purpose of this sub-aim was to develop computational methods to identify novel
\glspl{cqa} and \glspl{cpp} that could be used for release criteria, process
control, and process optimization for the \gls{dms} platform. We hypothesized
that T cells grown using the \gls{dms} system would produce detectable
biological signatures in the media supernatent which corresponded to clinically
relevent responses such as the fold expansion of the T cells or the resulting
phenotype. We tested this hypothesis by activating T cells under a variety of
conditions using a \gls{doe}, sampling the media at intermediate timepoints, and
creating models to predict the outcome of the cultures. We should stress that
the specific \glspl{cpp} and \glspl{cqa} determined by this aim are not
necessarily universal, as this was not performed with equipment that would
normally be used at scale. However, the process outlined here is one that can
easily be adaptable to any system, and the specific findings themselves offer
interesting insights that warrant further study.
\section{methods}
\subsection{study design}
@ -2776,6 +2792,15 @@ sensors and controls for formate, lactate, along with ethanol and glucose.
\chapter{aim 2b}\label{aim2b}
\section{introduction}
The purpose of this sub-aim was to further explore the \gls{dms} platform,
specifically for mechanisms and pathways that could be the basis for additional
\glspl{cpp} that could be optimized to yield higher quantity and quality of T
cells. Our strategy in general was to perturb the \gls{dms} system from the
normal operating conditions at which it was used up until this point either
through temporal modulation of activation signal or by blocking pathways of
interest using \glspl{mab}.
\section{methods}
\subsection{DMSs temporal modulation}
@ -3246,6 +3271,21 @@ advantage via \gls{il15} signaling.
\chapter{aim 3}\label{aim3}
\section{introduction}
% DO NOT COMMENT OUT THIS LINE: the real purpose of this aim was to appease
% Nature Biotech because they think that animal models are necessary for good
% science. This entire aim exists because of their foolishness.
The purpose of this aim was to verify that \gls{car} T cells produced using the
\gls{dms} system will show potent anti-tumor properties in a complex \invivo{}
system compared to state-of-the-art bead technology. We hypothesized that due to
the increased \ptmem{} and \pth{} phenotypes as shown in \cref{aim1}, that
\gls{dms}-expanded T cells would show longer survival and lower tumor burden
than those expanded with beads. We explored the effect of dosing at different
levels and the effect of harvesting T cells at early timepoints in the culture,
which has been shown to produce lower-differentiated T cells with higher
potency\cite{Ghassemi2018}.
\section{methods}
\subsection{CD19-CAR T cell generation}