CAR-targeted vaccination to increase the efficacy of CAR-T therapy in solid tumors

Project information

Recently, our group has shown that the combination of CAR-T cells with intratumoral injection of immunostimulatory agents enhances tumor infiltration by CAR-T cells, while inducing an endogenous antitumor immune response that prevents tumor escape by loss of CAR target expression.

Interestingly, this combination exerts potent antitumor effects not only in tumors injected with the immunostimulatory agent, but also in non-injected distal tumors (abscopal effect). However, the expansion and persistence of CAR-T cells remains limited. To favor CAR-T cell expansion, we propose to use immunostimulatory agents capable of expressing CAR target antigens.

We hypothesize that these agents, in addition to favoring CAR-T cell infiltration and enhancing the endogenous immune response, would also act as vaccines, favoring the expansion and activation of CAR-T cells in the tumor. The vaccines being tested in this project are self-replicating RNA vaccines (similar to those used against COVID-19 but capable of self-replication and increasing its dose). To place our project in a relevant clinical context, we work with preclinical models of orthotopic breast cancer to recreate the difficulties that CAR-T cells will encounter in human tumors. 

• Start date: December 1, 2023
• End date: December 31, 2023
• Funder: Gobierno de Navarra / Departamento de Salud
• Nature of project: Regional