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.

Trial watch: Peptide-based vaccines in anticancer therapy

“…267-269 In line with this notion, the vast majority of peptide-based vaccines tested in the clinic so far mediated limited, if any, therapeutic activity, despite being able to elicit tumor-targeting immune responses, at least to some degree. 118 The field is therefore moving along three non-mutually exclusive directions: (1) combining peptide-based vaccination with additional forms of (immuno)therapy, with the specific aim of reverting immunosuppression and enabling therapeutically relevant immune responses, 270-272 (2) targeting private antigenic epitopes that originate from mutations affecting only malignant cells (or sub-populations thereof), with PPV, 167,272-275 and (3) identifying specific patient populations that may obtain clinical benefit from the use of peptide-based vaccination. 174,254 Although the feasibility of PPV on a large scale remains unclear, we surmise combining some variants of peptide-based vaccination with potent immunostimulatory agents including immune checkpoint blockers and oncolytic viruses may be the key to unlock the true potential of this hitherto unrealized therapeutic modality.…”

neoANT-HILL: an integrated tool for identification of potential neoantigens

“…Cancer immunotherapy is rapidly advancing due to the progress in the understanding of the interaction between cancer and immune cells. Neoantigens are attractive candidates because these peptides can be used to design a personalized, efficient and safer cancer immunotherapy option (Guo et al, 2018). However, accurate prediction of neoantigens remains a challenge due to multiple factors such as antigen processing, HLA binding affinity, amino acid composition and expression level of the mutant peptide that must be considered (Ghorani et al 2017).…”

Role of lymph node stroma and microenvironment in T cell tolerance

“…124,125 Here we will focus on materials and methods designed to induce suppression and tolerance by delivery to the LN. 124,125 Here we will focus on materials and methods designed to induce suppression and tolerance by delivery to the LN.…”

“…These investigations have been extensively reviewed elsewhere and will not be discussed here. 124,125 Here we will focus on materials and methods designed to induce suppression and tolerance by delivery to the LN.…”