PhD Proposal by Miguel Armenta Ochoa

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Miguel Armenta Ochoa

BME PhD Proposal Presentation

Date: 2022-10-13
Time: 10:30 am
Location / Meeting Link: https://gatech.zoom.us/j/92689880726?pwd=czRkWkxyMmlOb1hVQjlDL0pWcFpVUT09

Committee Members:
Krishnendu Roy, Ph.D. (Advisor); Lawrence Boise, Ph.D.; Leslie Chan, Ph.D.; Erik Dreaden, Ph.D.; Gabe Kwong, Ph.D.

Title: Improving T Cell Manufacturing using Physiologically Inspired Approaches

Chimeric Antigen Receptor (CAR) T cell therapy is a revolutionary cancer immunotherapy where a patient’s own immune cells are harnessed to fight their disease. With initial FDA approval in 2017, there are now 6 approved therapies for various diseases: leukemia, lymphoma, and multiple myeloma. Initial response rates for the therapy have been encouraging, reaching around 80% remission depending on the product with some patients from the original clinical trials achieving remission for over 10 years. However, not all patients are so lucky, as the autologous- or patient derived- nature of the therapy leads to widely disparate patient outcomes. A central driving force for these discrepancies is the limited understanding of the cell manufacturing process and the lack of control over desired outcomes. By analyzing the differential characteristics of cell products administered to complete-responder vs. non-responder patients, the field has developed a better understanding as to what defines a high-quality cell product; notably, higher prevalence of helper (CD4+) and memory (naïve, stem-like, and central memory) subtypes is correlated with more complete responses in patients. Despite this knowledge, the cell manufacturing space has limited control to tune the culture process to maximize the expansion of these desired cell types. Therefore, the work proposed herein aims to leverage physiological cues and engineering solutions to better inform how individual culture process parameters influence the quality of manufactured cell products. Aim 1 strives to improve the fabrication process of Degradable Microscaffolds (DMSs), a novel T cell activation system, and then leverage this system to investigate the role that various activating ligands play on the yield and quality of cells. Aim 2 then seeks to employ the ERBI Breez, a feedback-controlled benchtop bioreactor, to mimic key microenvironmental cues seen in-vivo and to validate the effects of these cues on the expansion of multiple myeloma (MM) patient-derived CAR-T cells. Successful completion of this work could lead to improved patient outcomes and greater accessibility to the therapy as cost and manufacturing failures decrease.


  • Workflow Status: Published
  • Created By: Tatianna Richardson
  • Created: 09/30/2022
  • Modified By: Tatianna Richardson
  • Modified: 09/30/2022