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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.

SUBMITTER: Ho SY

PROVIDER: S-EPMC10056833 | biostudies-literature | 2023 Mar

REPOSITORIES: biostudies-literature

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Current Trends in Neoantigen-Based Cancer Vaccines.

Ho Szu-Ying SY Chang Che-Mai CM Liao Hsin-Ni HN Chou Wan-Hsuan WH Guo Chin-Lin CL Yen Yun Y Nakamura Yusuke Y Chang Wei-Chiao WC

Pharmaceuticals (Basel, Switzerland) 20230305 3

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 f ...[more]

PMID: 36986491

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Project description:Major advances in cancer treatment have emerged with the introduction of immunotherapies using blocking antibodies that target T-cell inhibitory receptors, such as programmed death-1 (PD-1) and cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4), known as immune checkpoints. However, most cancer patients do not respond to immune checkpoint blockade (ICB) therapies, suggesting the development of resistance mechanisms associated with either an insufficient number of preexisting tumor-specific T-cell precursors and/or inappropriate T-cell reactivation. To broaden clinical benefit, anti-PD-1/PD-1 ligand (PD-L1) neutralizing antibodies have been combined with therapeutic cancer vaccines based on non-mutant and/or mutant tumor antigens, to stimulate and expand tumor-specific T lymphocytes. Although these combination treatments achieve the expected goal in some patients, relapse linked to alterations in antigen presentation machinery (APM) of cancer cells often occurs leading to tumor escape from CD8 T-cell immunity. Remarkably, an alternative antigenic peptide repertoire, referred to as T-cell epitopes associated with impaired peptide processing (TEIPP), arises on these malignant cells with altered APM. TEIPP are derived from ubiquitous non-mutant self-proteins and represent a unique resource to target immune-edited tumors that have acquired resistance to cytotoxic T lymphocytes (CTLs) related to defects in transporter associated with antigen processing (TAP) and possibly also to ICB. The present review discusses tumor-associated antigens (TAAs) and mutant neoantigens and their use as targets in peptide- and RNA-based therapeutic cancer vaccines. Finally, this paper highlights TEIPP as a promising immunogenic non-mutant neoantigen candidates for active cancer immunotherapy and combination with TAA and mutant neoantigens. Combining these polyepitope cancer vaccines with ICB would broaden T-cell specificity and reinvigorate exhausted antitumor CTL, resulting in the eradication of all types of neoplastic cells, including immune-escaped subtypes.

Dataset Information

Current Trends in Neoantigen-Based Cancer Vaccines.

Publications

Current Trends in Neoantigen-Based Cancer Vaccines.

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