A novel chimeric antigen receptor (CAR) that increases CAR-T cell function has been engineered. Typically, a CAR is comprised of a targeting ligand capable of binding to a specific antigen, and at least one co-stimulatory signal domain (CSSD), such as 4-1BB or CD28, that enhances T cell effector functions. We have developed a new CSSD derived from the herpes virus mediator (HVEM) protein, which shows enhanced effector functions, and reduced levels of exhaustion when compared to 4-BB or CD28 CSSDs. We have demonstrated that CAR-T cells that incorporate the HVEM domain have improved activities in a solid tumor mouse model.
- Chimeric Antigen Receptor T Cell Bearing Herpes Virus Entry Mediator Co-stimulatory Signal Domain Exhibits High Functional Potency Mol Ther Oncolytics. 2019 Mar 23;14:27-37