Tailoring nanovectors for optimal neoantigen vaccine efficacy

The primary objective of neoantigen vaccines is to elicit a robust anti-tumor immune response by generating neoantigen-specific T cells that can eradicate tumor cells. Despite substantial advancements in personalized neoantigen prediction using next-generation sequencing, machine learning, and mass spectrometry, challenges remain in efficiently expanding neoantigen-specific T cell populations in vivo. This challenge impedes the widespread clinical application of neoantigen vaccines. Nanovector-based neoantigen delivery systems have emerged as a promising solutions to this challenge. These nanovectors offer several advantages, such as enhanced stability, targeted intracellular delivery, sustained release, and improved antigen-presenting cell (APC) activation. Notably, they effectively deliver various neoantigen vaccine formulations (DC cell-based, synthetic long peptide (SLP)-based or DNA/mRNA-based) to APCs or T cells, thereby activating both CD4⁺ T and CD8⁺ T cells. This ultimately induces a specific anti-tumor immune response. This review focuses on recent innovations in neoantigen vaccine delivery vectors. We aim to identify optimal design parameters for vectors tailored to different neoantigen vaccine types, with an emphasis on enhancing the tumor microenvironment and stimulating the production of neoantigen-specific cytotoxic T cells. By maximizing the potential of these delivery systems, we aim to accelerate the clinical translation of neoantigen nanovaccines and advance cancer immunotherapy.