Current Trends in Neoantigen-Based Cancer Vaccines

Abstract

Cancer immunotherapies are treatments that use drugs or cells to activate patients' own immune systems against cancer cells. Among them, cancer vaccines have recently been rapidly developed. Based on tumor-specific antigens referred to as neoantigens, these vaccines can be in various forms such as messenger (m)RNA and synthetic peptides to activate cytotoxic T cells and act with or without dendritic cells. Growing evidence suggests that neoantigen-based cancer vaccines possess a very promising future, yet the processes of immune recognition and activation to relay identification of a neoantigen through the histocompatibility complex (MHC) and T-cell receptor (TCR) remain unclear. Here, we describe features of neoantigens and the biological process of validating neoantigens, along with a discussion of recent progress in the scientific development and clinical applications of neoantigen-based cancer vaccines.

Keywords: T-cell response; cancer neoantigen; immune system; neoantigen vaccine.

Figure 1

Identification of candidate cancer neoantigens and validation for functional neoantigens. Samples of both the normal and tumor cells from the same patient are collected for whole-exome DNA sequencing or RNA sequencing. Significant variants in protein-encoding regions and expressed mutations can be identified. Two general methods are applied to predict the MHC binding: in silico computational predictions and mass spectrum analyses. Enzyme-linked immunosorbent spot (ELISPOT), supported lipid bilayer (SLB)-based T-cell activation assays, and DNA barcode-based pMHC tetramer assays are used for functional validation.

Figure 2

Methods for neoantigen delivery. Target DNA and mRNA molecules can be delivered by adenoviral vectors and liposomes to dendritic cells (DCs) for neoantigen production and presentation. Alternatively, neoantigens can be given in the form of peptides, which can be up taken by DCs in vivo.

Figure 3

Applications of personalized cancer immunotherapy. Cancer immunotherapies can act through active immunity or passive immunity. The active immunity approach aims to activate the human immune system to attack tumor cells, such as the injection of long peptide or mRNA neoantigen vaccines. The passive immunity approach is to apply activated immune cells, antibodies, or cytokines to kill tumor cells.