Innovative Approaches to Enhance Chimeric Antigen Receptor (CAR) T-Cell Potency Using Quiescent T Cells
Abstract
My research focuses on developing Chimeric Antigen Receptor (CAR) T cells for adoptive immunotherapy. The goal of the research is to enhance the efficacy of CAR T therapy by developing potent CAR T cells. Another goal of this research is to shorten the CAR T manufacturing period to increase the availability of this therapy in resource constraint health care settings, as well those patients with rapidly progressive disease. CAR T cells are generated by transducing activated T cells with lentiviral vectors and expanding their progeny over 9-14 days. T cells progressively differentiate over time. Transducing non-activated T cells with CAR will preserve the intrinsic stem-like properties of naive and memory T cells. This approach will yield CAR T cells with enhanced replicative capacity, engraftment, and in vivo activity. The purpose of this work is to determine the optimal T cell subset and corresponding optimal costimulatory domain for CAR when it is expressed in quiescent T cells. The scope of this research is that CAR T cells generated by transducing quiescent T cells will preserve the intrinsic stem-like properties of naive and memory T cells. We found that spare respiratory capacity, SRC, is replenished in ICOSZ as well as BBZ CAR T cells. We also demonstrated that naive T cell subsets have increased persistence with decreased tumor burden when BBZ CAR T cells is used.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jul 01, 2022
- Accession Number
- AD1190551
Entities
People
- Saba Ghassemi
Organizations
- University of Pennsylvania