Immune targeting of three independent suppressive pathways (TIGIT, PD-L1, TGFβ) provides significant antitumor efficacy in immune checkpoint resistant models.

ABSTRACT: Immune checkpoint blockade (ICB) therapy, while groundbreaking, must be improved to promote enhanced durable responses and to prevent the development of treatment-refractory disease. Cancer therapies that engage, enable, and expand the antitumor immune response will likely require rationally designed combination strategies. Targeting multiple immunosuppressive pathways simultaneously may provide additional therapeutic benefit over singular targeting. We therefore hypothesized that the use of two molecules which inhibit three independent, but overlapping, pathways (TIGIT:CD155, PD-1/PD-L1, and TGFβ) would provide significant antitumor efficacy in the syngeneic ICB resistant colorectal tumor model MC38 expressing human carcinoembryonic antigen (CEA) in CEA transgenic mice. This novel combina

SUBMITTER: Franks SE 

PROVIDER: S-EPMC9542338 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature