Neoantigen Driven Eradication of Immune-Reprogrammed Ovarian Cancer

Immunotherapy and Personalized Vaccines

Dwayne Stupack (UCSD)

Stephen Schoenberger (LJI)

David Schlaepfer (UCSD)

One approach to treating tumors uses intravenous therapies that help the immune system. This works in many cancers, however, this approach does not always work, and can fail with time as tumors find ways to avoid the immune system – even shutting off its ability to attack tumors. Our ability to avoid a “shut down” of the immune system in ovarian cancer was strengthened by studies showing that an oral drug called a FAK inhibitor, which targets a gene that is altered in 3 of 4 ovarian cancer patients. The drug has broad benefits to the immune system. Importantly, FAK can be combined with other immunotherapies. A second type of immunotherapy in development is a cell-based therapy that uses vaccination against unique features of the tumor. While very precise, and potentially very potent, this approach is highly vulnerable to the ability of tumors to shut off the tumor-attack part of the immune system. This proposal will test a new idea; treat tumors to block their ability to shut off the immune response with the FAK drug first, then expose them to a vaccine engineered directly against them. The studies here will use a mouse model that recapitulates HGSOC determine [1]- which features are best to target, [2a] Can we use vaccination in a test tube and deliver the immune response to a more immune-active mouse conditioned by FAK, and [2b] For tumors treated with chemotherapy and surgery, can we then treat them with FAK drugs together with vaccination to allow the immune system to get rid of residual disease. A lot of groundwork has gone in to reach this point, and we are now set to finish the studies within a year.