Can Personalized Neoantigens Raise the T Cell Bar?

Abstract

Ott et al. report the results of a phase 1B study in which a personalized neoantigen vaccine was combined with programmed death receptor-1 blockade in patients with advanced cancers. The study provides a framework for combinatorial vaccine therapies that could mount robust T cell responses, enhance tumor killing, and provide clinical benefit.

Figure 1.. Immune Responses in Patients Responding to Combinatorial Therapy with Nivolumab and a Personalized Vaccine Containing SLPs Corresponding to Patient-Specific Tumor Neoantigens

These “responders” displayed a higher baseline tumor mutation burden (TMB), better peripheral T cell quality (specifically increased effector memory CD8+ T cells), a more restricted T cell repertoire, and higher levels of stem-like memory T cell signatures in the tumor. Cytotoxic neoantigen-specific T cells were detected in peripheral blood and were able to traffic into the tumor to recognize and kill tumor cells. Epitope spreading was also detected likely as a result of vaccine-induced, T cell-mediated tumor cell death causing the release of neoantigens. Further detailed studies should characterize the immune response in non-responders in order to improve response rates.