No CAR access

Chimeric antigen receptor (CAR)-T cells often fail against solid tumors due to their immunosuppressive microenvironment. A study led by Ludwig Lausanne’s Melita Irving, George Coukos and Evripidis Lanitis explored the limitations of second-generation (2G) murine CAR-T cells targeting the vascular endothelial growth factor receptor-2 (VEGFR-2), which plays a central role in the development of new blood vessels that feed tumors. Such CAR-T cells have been shown in previous studies to have limited efficacy as a monotherapy. Melita, George, Evripidis and their colleagues reported in an August paper in the Journal for ImmunoTherapy of Cancer that resistance to the therapy stems not from the tumor’s suppression of VEGFR-2 expression—a common mechanism of escape—but from its elevated production of VEGF-A, the protein ligand that binds VEGFR-2. They show that VEGF-A undermines the therapy by blocking CAR-T cells’ engagement with their target antigen—the first observation of such a mechanism of resistance to CAR-T cell therapy. Administering antibodies to VEGF-A enabled CAR-T control of tumors and boosted persistence of the CAR-T cells in mouse models of melanoma.

This article appeared in the February 2022 issue of Ludwig Link. Click here to download a PDF (1 MB).


You are now leaving Ludwig Cancer Research's website and are going to a website that is not operated by the association. We are not responsible for the content or availability of linked sites. Do you wish to continue?