An empirical antigen selection method identifies neoantigens that either elicit broad anti-tumor T cell responses or drive tumor growth.

Neoantigens are critical targets of anti-tumor T cell responses. The ATLAS{trade mark, serif} bioassay was developed to identify neoantigens empirically by expressing each unique patient-specific tumor mutation individually in E. coli, pulsing autologous dendritic cells in an ordered array, and testing the patient\u27s T cells for recognition in an overnight assay. Profiling of T cells from lung cancer patients revealed both stimulatory and inhibitory responses to individual neoantigens. In the murine B16F10 melanoma model, therapeutic immunization with ATLAS-identified stimulatory neoantigens protected animals, whereas immunization with peptides associated with inhibitory ATLAS responses resulted in accelerated tumor growth and abolished efficacy of an otherwise-protective vaccine. A planned interim analysis of a clinical study testing a poly-ICLC adjuvanted personalized vaccine containing ATLAS-identified stimulatory neoantigens showed that it is well-tolerated. In an adjuvant setting, immunized patients generated both CD4+ and CD8+ T cell responses, with immune responses to 99% of the vaccinated peptide antigens