Chimeric antigen receptor (CAR) T cells provide great efficacy in B cell malignancies. However, improved CAR T cell therapies are still needed. Here, we engineered tumor-targeted CAR T cells to constitutively express the immune-stimulatory molecule CD40 ligand (CD40L) and explored efficacy in different mouse leukemia/lymphoma models. We observed that CD40L+ CAR T cells circumvent tumor immune escape via antigen loss through CD40/CD40L-mediated cytotoxicity and induction of a sustained, endogenous immune response. After adoptive cell transfer, the CD40L+ CAR T cells displayed superior antitumor efficacy, licensed antigen-presenting cells, enhanced recruitment of immune effectors, and mobilized endogenous tumor-recognizing T cells. These effects were absent in Cd40−/− mice and provide a rationale for the use of CD40L+ CAR T cells in cancer treatment. Display omitted •CD40L+ CAR T cells kill antigen-negative tumor cells through CD40/CD40L interactions•CD40L+ CAR T cells improve antitumor response compared with second-generation CAR T cells•CD40L+ CAR T cells license APCs in vivo to aid in antitumor response•Licensed APCs prime non-CAR T cells to recognize tumor cells and produce cytokines Kuhn et al. engineer tumor-targeted CAR T cells to constitutively express CD40L. Through direct CD40/CD40L-mediated cytotoxicity and indirect induction of an immune response by enhancing recruitment and activation of immune effectors, the CD40L+ CAR T cells overcome tumor immune escape via antigen loss.