Transcription Control of Exhaustion Program in Car T-Cell Therapy
Abstract
The proposed research plan directly addresses the urgent need for novel therapies by developing the next generation of targeted T cells with chimeric antigen receptors (CARs) for use in therapy of pancreas cancer. The significance of our new strategy aimed at optimizing CAR T cell therapy is emphasized by the lack of clinical success in solid tumors. This project layout the strategy of armoring CAR-T cells with genetic modifications in transcriptional master regulators that control T cell exhaustion and/or longevity to generate a long-lasting response against the tumor. Utilizing a clinically relevant immune competent endogenous mouse model of pancreatic cancer, we will assess the effect of enhanced armored CAR-T cells on the tumor and how their function will persist compared with unmodified CAR-T. Defining factors that would allow CAR T cells to be genetically"reprogrammed" to maintain an active state is critical for successful use of CAR T cells for patients with pancreatic cancer who currently lack other treatment options. The core discovery driving methods and technical innovations are mutually synergistic and thus will efficiently spearhead my research and provide collaborative opportunities thus enhance prospects of my research and career development
Document Details
- Document Type
- Technical Report
- Publication Date
- Dec 01, 2022
- Accession Number
- AD1203888
Entities
People
- Pawel K Mazur
Organizations
- The University of Texas MD Anderson Cancer Center