Using virally-mediated genetic reprogramming may be key to creating metabolically robust CAR T cells for use in solid tumor immunotherapy. Several target genes including Ppargc1a, Tfam, Nrf2, and ERRalpha, have been identified as overexpressing in T cells and promoting mitochondrial biogenesis, a crucial component of cellular metabolic fitness.
Description
Immunotherapy is a paradigm-shifting treatment for advanced cancers. One type of immunotherapy at the forefront of the field is the use of chimeric antigen receptor (CAR) T cells to genetically redirect T cells to tumor targets. CAR T cell therapy has been remarkably effective in blood cancers but has yet to yield positive results in solid tumors due to the immunosuppressive microenvironment within the tumor, which represses T cell activity via chronic activation and metabolic destruction in a process deemed T cell ‘exhaustion’. To reap the benefits that this treatment has yielded for hematologic malignancies, CAR T cells will need to be more metabolically durable in order to perform in the microenvironment of solid tumors.
Applications
• Promote metabolic function in and fitness in CAR T cells
• CAR T cell therapy for solid tumors
Advantages
• Promotes overall health of the T cell
• Higher transcriptional activity compared to non-engineered genes
• Resistant to negative regulation
Invention Readiness
In vivo status
IP Status
https://patents.google.com/patent/US11583555B2Related Publication(s)
Scharping, N. E., Menk, A. V., Moreci, R. S., Whetstone, R. D., Dadey, R. E., Watkins, S. C., Ferris, R. L., & Delgoffe, G. M. (2016). The Tumor Microenvironment Represses T Cell Mitochondrial Biogenesis to Drive Intratumoral T Cell Metabolic Insufficiency and Dysfunction. Immunity, 45(2), 374–388. https://doi.org/10.1016/j.immuni.2016.07.009
