ARTICLE | Targets & Mechanisms

Personalized tumor vaccines

Personalized tumor vaccines derived from tumor-specific mutant epitopes

January 29, 2015 8:00 AM UTC

Although the jury is in on the role of PD-1 inhibitors in enabling T cell activation in cancer, it is still unclear which tumor epitopes are targeted by the T cells or whether those epitopes can be exploited therapeutically. New findings show the T cells bind to tumor specific mutant antigens that arise in individual tumors, and suggest the antigens could be used to create personalized vaccines that potentiate checkpoint therapies.The findings were produced in independent studies by two separate groups: one at Washington University in St. Louis, and the other at the Genentech Inc. unit of Roche.

The process by which the immune system controls and shapes tumors - known as immunoediting - involves three stages; elimination, equilibrium and escape. During elimination, the immune system destroys tumor cells by targeting tumor-specific antigens. In the equilibrium phase, sporadic tumor cells begin to avoid destruction by altering their antigenic profiles through mutation. Finally, in the escape phase, the newly sculpted tumor cells suppress the immune cells in their microenvironment and grow rampantly.Although immunoediting occurs in human tumors as a response to immunotherapy, no direct linkage has been made between checkpoint therapies and any tumor-specific mutant antigens. However, a recent study at Memorial Sloan Kettering Cancer Center on melanoma patients treated with anti-CTLA4 therapy identified a common neoepitope signature among different patients' tumors...