Tumor Burden Dictates the Neoantigen Features Required to Generate an Effective Cancer Vaccine

Abstract

Tumor neoantigens (nAg) represent a promising target for identification of 2 nAgs able to induce CD8þ T cell–mediated cancer immunotherapy. The identification of nAgs that can gen-tumor rejection. They were both active as individual nAgs in a erate T-cell responses and have therapeutic activity has been setting of prophylactic vaccination, although to different extents. challenging. Here, we sought to unravel the features of nAgs However, the efficacy of these single nAgs was lost in a setting of required to induce tumor rejection. We selected clinically validated therapeutic vaccination in tumor-bearing mice. The presence of Great Ape–derived adenoviral vectors (GAd) as a nAg delivery CD4þ T-cell help restored the efficacy for only the most expressed of system for differing numbers and combinations of nAgs. We the two nAgs, demonstrating a key role for CD4þ T cells in assessed their immunogenicity and efficacy in murine models of sustaining CD8þ T-cell responses and the necessity of an efficient low to high disease burden, comparing multi-epitope versus mono-recognition of the targeted epitopes on cancer cells by CD8þ T cells epitope vaccines. We demonstrated that the breadth of immune for an effective antitumor response. This study provides insight into response is critical for vaccine efficacy and having multiple immuunderstanding the determinants of nAgs relevant for effective nogenic nAgs encoded in a single vaccine improves efficacy. The treatment and highlights features that could contribute to more contribution of each single neoantigen was examined, leading to the effective antitumor vaccines.