CD40 Ligand-Modified Chimeric Antigen Receptor T Cells Enhance Antitumor Function by Eliciting an Endogenous Antitumor Response

Publication date: 18 March 2019Source: Cancer Cell, Volume 35, Issue 3Author(s): Nicholas F. Kuhn, Terence J. Purdon, Dayenne G. van Leeuwen, Andrea V. Lopez, Kevin J. Curran, Anthony F. Daniyan, Renier J. BrentjensSummaryChimeric 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.Graphical Abstract
Source: Cancer Cell - Category: Cancer & Oncology Source Type: research