Joseph Fraietta, PhD, on Investigating Molecular Pathways of CAR T-Cell Resistance


The assistant professor of microbiology at Penn Medicine discussed research into characterizing type 1 interferon and EGR2 signaling and their effects on CAR T-cell activation.

“We've identified the CAR T-cells during their ongoing activation. So, if you have antigen there that's just present and [the cells] keep getting hit with antigen, they sort of self-perpetuate this type 1 interferon signaling. And we found that it'sactually counterproductive in our context, and that persistent and ongoing type 1 interferon signalingactually hampersantitumor function.”

Researchers from University of Pennsylvania have elucidated the role that type 1 interferon plays in affecting antitumor function of chimeric antigen receptor (CAR) T-cells and how modulating the EGR2 transcription factor or using recombinant interferon-β may improve the affected antitumor response.

These findings were presented at the American Society of Gene and Cell Therapy (ASGCT) 2023 Annual Meeting, held May 16-20, in Los Angeles, California, by Joseph Fraietta, PhD, assistant professor, microbiology, school of medicine, Penn Medicine, University of Pennsylvania. CGTLive spoke with Fraietta to learn more about the findings and how they could potentially help inform future research or clinical care. He discussed the research he conducted and how the findings seemed to be applicable across multiple types of cancers. He also noted the potential ability to look at EGR2 signaling as a biomarker for T-cell fitness to predict CAR T-cell therapy failure and even patient survival. He stressed why it is important to closely, at a molecular level, investigate mechanisms of CAR T-cell resistance to be able to improve outcomes with the use of these and other cell therapies.

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

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