Engineering Universal Chimeric Antigen Receptors (CARs) for Cancer Therapy

Presenter: Dr. Jason Lohmueller

The Lohmueller laboratory is using synthetic biology approaches to develop next-generation adoptive cell therapeutics (ACT) to treat cancer. Specifically, they are seeking to genetically re-program patients' T cells to improve their tumor-targeting specificity and to combat current barriers of therapy such as immune inhibitory signals in the tumor microenvironment and cell-intrinsic limits to T cell persistence and function. A fundamental part of this work and the focus of the seminar is developing “universal” chimeric antigen receptors (CAR) that can be targeted to any cell surface antigen of interest by co-administered tumor-targeting antibodies. Universal CARs have several potential advantages over standard CAR T cell therapy including the ability to control CAR 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.

Background reading:

• Post-translational covalent assembly of CAR and synNotch receptors for programmable antigen targeting
• mSA2 affinity-enhanced biotin-binding CAR T cells for universal tumor targeting
• Current modalities in cancer immunotherapy: Immunomodulatory antibodies, CARs and vaccines