Current progress in neoantigen-based dendritic cell vaccines for solid tumors.

Abstract

Immunotherapy, particularly immune checkpoint inhibitors (ICIs) programmed death-ligand 1/programmed death-1 (PD-L1/PD-1) and cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4), has heralded a new era of tumor treatment. Although ICIs have clinical benefits, their complex heterogeneity and diverse resistance mechanisms critically limit their efficacy. Neoantigens, arising from tumor-specific alterations, offer novel targets for individualized immunotherapy, because of their high immunogenicity and tumor specificity. In the past decade, neoantigen-based tumor vaccines have been demonstrated to be a promising immunotherapy strategy to prime the tumor-specific immune response. These therapeutic vaccines include peptide vaccines, nucleic acid vaccines, and dendritic cell (DC) vaccines, and are categorized according to the neoantigen source and delivery method. In vivo, neoantigens are processed and presented by antigen-presenting cells (APCs) via the peptide-Major Histocompatibility Complex (pMHC) for T cell recognition, thereby triggering specific immune responses. Because DCs, the most potent APCs, play crucial roles in antitumor immunity, neoantigen-based DC vaccines provide a promising therapeutic strategy. A series of global clinical trials are exploring the safety, feasibility, and efficacy of neoantigen-based DC vaccines in tumors. This review focuses on current progress in clinical research on neoantigen-based DC vaccines in the treatment of solid tumors.