Joseph Fraietta, PhD, on Achieving a Deeper Understanding of CAR T-Cell Therapy

“We've identified that EGR2 plays a role in promoting an inhibitory type 1 interferon response, but we still need to understand more about the mechanistic underpinnings of this - what are the molecular mechanisms at a very deep level that allow EGR2 to control type 1 interferon signaling, and how does this interaction occur with other signaling pathways? I think wereally only scratched the surface there.”

New research from University of Pennsylvania has elucidated the role that type 1 interferon plays in affecting antitumor function of chimeric antigen receptor (CAR) T-cells. The researchers also investigated effects ofmodulating the EGR2 transcription factor or using recombinant interferon-β to improve antitumor response.

The research was presented by Joseph Fraietta, PhD, assistant professor, microbiology, school of medicine, Penn Medicine, University of Pennsylvania, at the American Society of Gene and Cell Therapy (ASGCT) 2023 Annual Meeting, held May 16-20, in Los Angeles, California. CGTLive spoke with Fraietta to learn more about further research that he would like to see conducted with EGR2 and type 1 interferon. He also discussed potential applications of looking at the biomarkers, such as using them to predict outcomes of CAR T-cell therapy treatment. He discussed the findings that EGR2 gene signature could predict CAR T-cell therapy failure and patient survival in chronic lymphocytic leukemia and acute lymphoblastic leukemia to start with, but this may be applicable across different cancers. He stressed how the new research has only scratched the surface of understanding and how deeper investigations into these pathways are needed.

Click here to read more coverage of the ASGCT 2023 meeting.

REFERENCE

Fraietta JA. Armoring T-cells. Presented at: ASGCT 2023 Annual Meeting; May 16-20; Los Angeles, California.