Nate Dwarshuis

BME PhD Proposal Presentation

Date: May 7th, 2019

Time: 12:00 PM

Location: EBB 5029

Advisor: Krishnendu Roy (Georgia Institute of Technology)

Committee Members:

Madhav Dhodapkar (Emory University)

Melissa Kemp (Georgia Institute of Technology)

Wilbur Lam (Georgia Institute of Technology)

Sakis Mantalaris (Georgia Institute of Technology)

Title: Optimizing T Cell Manufacturing and Quality Using Functionalized Microcarriers

Abstract/Summary:

Adoptive cell therapies (ACT) using chimeric antigen receptor (CAR) T cells have shown promise in treating cancer, but manufacturing large numbers of high quality cells remains challenging. Critically, current T cell expansion technologies only partially recapitulate the in vivo microenvironment found in the human lymph nodes. In these organs, T cells expand at high cell density with autocrine/paracrine signaling, as well as signals from the extracellular matrix (ECM). Here we propose a T cell expansion system using degradable gelatin microcarriers functionalized with anti-CD3 and anti-CD28 monoclonal antibodies (mAbs), which address several of these shortcomings by providing a 3D surface on which T cells can cluster at high cell density and remain in contact with ECM components.

The overall objective of this proposal will be to develop this microcarrier platform into a controllable process that can conceivably be used in industry. We will do this in three aims: 1) Develop a novel microcarrier platform and assess its performance relative to current state-of-the-art T cell expansion technology, 2) optimize the microcarrier system for in vivo performance using a design of experiments (DOE) approach, and 3) characterize microcarrier- expanded T cell of differing performance using multiomics techniques to generate predictive models. The result of these three aims will be a platform for expanding T cells and an accompanying set of mathematical models that can be used to predict and control process outcomes.