| First Author | Kuhn NF | Year | 2019 |
| Journal | Cancer Cell | Volume | 35 |
| Issue | 3 | Pages | 473-488.e6 |
| PubMed ID | 30889381 | Mgi Jnum | J:347521 |
| Mgi Id | MGI:6285467 | Doi | 10.1016/j.ccell.2019.02.006 |
| Citation | Kuhn NF, et al. (2019) CD40 Ligand-Modified Chimeric Antigen Receptor T Cells Enhance Antitumor Function by Eliciting an Endogenous Antitumor Response. Cancer Cell 35(3):473-488.e6 |
| abstractText | 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. |
