Neoantigens: promising targets for cancer therapy

Abstract

Recent advances in neoantigen research have accelerated the development and regulatory approval of tumor immunotherapies, including cancer vaccines, adoptive cell therapy and antibody-based therapies, especially for solid tumors. Neoantigens are newly formed antigens generated by tumor cells as a result of various tumor-specific alterations, such as genomic mutation, dysregulated RNA splicing, disordered post-translational modification, and integrated viral open reading frames. Neoantigens are recognized as non-self and trigger an immune response that is not subject to central and peripheral tolerance. The quick identification and prediction of tumor-specific neoantigens have been made possible by the advanced development of next-generation sequencing and bioinformatic technologies. Compared to tumor-associated antigens, the highly immunogenic and tumor-specific neoantigens provide emerging targets for personalized cancer immunotherapies, and serve as prospective predictors for tumor survival prognosis and immune checkpoint blockade responses. The development of cancer therapies will be aided by understanding the mechanism underlying neoantigen-induced anti-tumor immune response and by streamlining the process of neoantigen-based immunotherapies. This review provides an overview on the identification and characterization of neoantigens and outlines the clinical applications of prospective immunotherapeutic strategies based on neoantigens. We also explore their current status, inherent challenges, and clinical translation potential.

Emerging Trends in Nano-Driven Immunotherapy for Treatment of Cancer

“…Cancer cells differ from normal cells in that they express a variety of tumour-associated antigens (TAAs). Specialised TAAs such as proteins with altered post-translational modifications or encoded by chromosomal abnormalities, and mutant gene products have the capability to form entirely in cancer cells and are referred to as “neoantigens” [ 11 ]. In other words, neoantigens can be referred to as non-self-proteins that are produced by tumour cells.…”

Computational Methods in Immunology and Vaccinology: Design and Development of Antibodies and Immunogens

“…The identification and targeting of neoepitopes is one of the most actively evolving fields of cancer immunotherapy aiming at the development of neoantigen based vaccines and T-cell based therapies. − Current strategies for the identification of neoantigens rely on advanced sequencing techniques, including next-generation sequencing or -omics data aimed at individuating peptides distinguished from self-peptides. These are coupled with computational tools including those that we describe below for general purpose prediction of T-cell epitopes immunogenicity. ,− …”

Mini‐review: Immunology in ovarian cancer

“…40,51,52 Immunotherapies should also aim to increase the number of neoantigens to allow T cells to target tumor cells. 53 For example, chemotherapy, radiotherapy, and molecular targeted therapies kill tumor cells and produce neoantigens. The addition of chemotherapies or molecular targeted therapies with the PD-L1/PD-1 blockade has been also evaluated.…”

“…Immunotherapies should also aim to increase the number of neoantigens to allow T cells to target tumor cells 53 . For example, chemotherapy, radiotherapy, and molecular targeted therapies kill tumor cells and produce neoantigens.…”