This event will be held virtually on zoom. Check email for zoom link or email ksas@seas.upenn.edu.

CAR T cells—T cells engineered to express a chimeric antigen receptor that redirects their function to a specific antigen—have proven to be an effective therapy for certain B cell cancers, but many issues remain in order to apply CAR T cells to a broader range of cancers. The activity of CAR T cells can be  modulated by varying their co-stimulatory domains. Most CARs use co-stimulatory domains from natural proteins such as 41BB or CD28, each of which contains motifs that recruit unique signaling molecules and elicit a corresponding T cell response. One strategy to achieve increased control over T cell function is to engineer synthetic co-stimulatory domains composed of novel combinations of motifs from natural co-stimulatory proteins. We constructed libraries of CARs containing synthetic co-stimulatory domains and screened these library in primary human T cells for the ability to promote proliferation, degranulation, and memory formation. The results of the screens give insights into how signaling motifs dictate cell function and offer clues on how to engineer co-stimulatory domains that promote desired CAR T cell functions.