Engineering universal chimeric antigen receptors (CARs) for cancer therapy

Chimeric antigen receptors (CARs) are artificial T cell receptors that re-target patients’ T cells to specifically recognize and kill tumor cells. CAR T cell therapies targeting CD19 and now BCMA are FDA-approved and revolutionizing treatment of refractory B cell cancers. However, there are several limitations to current treatments and the application of CAR T cells to treat additional diseases, including toxicities and antigen-loss leading to relapse. To address these issues, we and others have developed “universal” CARs for which antigen-specificity is directed by one or more co-administered tumor-targeting antibodies. Universal CARs have several technical advantages over standard CAR T cell therapy including the ability to control activity by antibody dose, the ability to target multiple antigens on the same tumor to limit relapse, and the ability to be used across different cancer indications. Universal CAR T cells also come with unique technical challenges. In the seminar I will introduce universal CAR T cell design and mechanism of action, highlighting the universal “SNAP-CAR” technology developed in my lab and review other universal CARs in development. Finally, I will discuss technical challenges and future directions for universal CAR T cells including new mechanisms of conditional control potentially leading to greater tumor-targeting specificity.

Learning Objectives:

1. Define “universal CARs” and describe their mechanism of action.

2. Explain current challenges in CAR T cell therapy.

3. Describe potential benefits and challenges of therapy using T cells engineered with universal CARs.