CAR T-cell + oncolytic vesicular stomatitis virus

CAR T-cell + oncolytic vesicular stomatitis virus is an experimental combination immunotherapy in which chimeric antigen receptor (CAR) T cells are used both as cytotoxic effectors and as carrier cells for an oncolytic vesicular stomatitis virus (VSV), typically an attenuated mutant such as VSVΔ51, to enhance antitumor activity against solid tumors.[1][5][7] The VSV particles are specifically loaded onto the surface of CAR T cells ex vivo, often by engineering the CAR ectodomain (for example with CR2/3 domains of the low-density lipoprotein receptor, the entry receptor for VSV mutants) to increase viral binding and loading; once infused, the CAR T cells traffic to tumors, release VSV into the tumor microenvironment, and simultaneously receive tonic activation via cross-linking between VSV glycoprotein and the CAR, improving proliferation, metabolic fitness, and effector function.[5][7] Within tumors, oncolytic VSV directly lyses malignant cells and induces a proinflammatory milieu that enhances CAR T-cell infiltration, overcomes local immunosuppression, and promotes systemic antitumor immunity, leading to superior tumor control and survival compared with either modality alone in preclinical glioblastoma and other solid tumor models.[1][3][5][7] This strategy is being explored at the preclinical stage by academic groups as a platform approach for solid tumor indications, but it does not yet correspond to a defined commercial product.

Other names

CAR-T + oncolytic VSVCAR T cells loaded with oncolytic vesicular stomatitis virusCAR T-cell VSVΔ51CR2/3–CAR-T VSVΔ51