632. Sustained Function and Enhanced Replicative Capacity of Anti-Tumor CD4+ Effectors by Enforced Co-Stimulation

Abstract

Optimal T-Cell activation for cytokine production, expansion and retention of effector functions requires multiple signals provided by co-stimulatory receptor signaling together with TCR-CD3 complex signaling. A chimeric antigen receptor (CAR) in our original redirected cytolytic T cells (CTLs) contains just a CD3z signal alone (Kahlon KS et al., 2004. Cancer Research), which may not be able to induce a full immune response in targeting tumors that rarely express costimulatory molecules. To circumvent this limitation, we improve the current CAR by addition of the cytoplasmic domain of CD28 and 4-1BB co-stimulator receptors.