Neoantigen Vaccine Delivery for Personalized Anticancer Immunotherapy

Abstract

Cancer neoantigens derived from random somatic mutations in tumor tissue represent an attractive type of targets for the cancer immunotherapies including cancer vaccine. Vaccination against the tumor-specific neoantigens minimizes the potential induction of central and peripheral tolerance as well as the risk of autoimmunity. Neoantigen-based cancer vaccines have recently showed marked therapeutic potential in both preclinical and early-phase clinical studies. However, significant challenges remain in the effective and faithful identification of immunogenic neoepitopes and the efficient and safe delivery of the subunit vaccine components for eliciting potent and robust anticancer T cell responses. In this mini review, we provide a brief overview of the recent advances in the development of neoantigen-based cancer vaccines focusing on various vaccine delivery strategies for targeting and modulating antigen-presenting cells. We discuss current delivery approaches, including direct injection, ex vivo-pulsed dendritic cell vaccination, and biomaterial-assisted vaccination for enhancing the efficiency of neoantigen vaccines and present a perspective on future directions.

Keywords: cancer immunotherapy; cancer vaccine; dendritic cell; in vitro transcribed mRNA; nanoparticle; neoantigen; synthetic long peptide; vaccine delivery.

Figure 1

Schematic illustration of the process of neoantigen discovery, vaccine manufacturing and formulation, and vaccination in patients. The first step for developing neoantigen cancer vaccine involves the identification of mutated tumor specific antigens by whole exome/transcriptome sequencing and prediction of immunogenic MHC epitopes. Next, neoantigen vaccines (e.g., SLP and mRNA) are manufactured and formulated for efficient delivery to secondary lymphoid organs (e.g., lymph node), where neoantigen vaccines are captured by APCs and presented to effector immune cells including CD8⁺ or CD4⁺ T cells. Various delivery strategies have been developed to achieve an effective and safe neoantigen-based cancer vaccine. Abbreviations: SLP, synthetic long peptide; DC, dendritic cell; APC, antigen-presenting cell; MHC, major histocompatibility complex.