The mortality related to cancer is rapidly increasing globally, reflecting the changes within the frequency and distribution of major risk factors of cancer. Over the past few decades, conventional treatments (e.g., surgery, radiation, and chemotherapies) disease prevention and diagnosis have made a significant impact on the overall survival rate of cancer patients and quality of life but the majority of malignancies remain incurable. Personalized cancer vaccine recently emerges as a promising new cancer treatment.

The development of next-generation sequencing technologies and a detailed map of the cancer mutanome offers a unique opportunity to understand how specific genetic events contribute to cancer initiation and progression and to develop a personalized cancer vaccine. New technologies are aiming to help the immune system identify and attack tumors. Significant experimental efforts in basic cancer immunology laboratories have put foundational details regarding cancer cell–immune system interactions, eventually validating the neoantigen concept.

Research has led to the identification of self-tumor antigens, which have been grouped into three categories: tumor-associated antigens, tumor-specific antigens, and cancer-testis antigens. TAAs are antigens overexpressed by cancer cells than normal tissues. TSAs are those specifically expressed only in cancer cells and CTAs are expressed, besides tumor cells, only in germline tissues and trophoblastic cells. Tumor-specific antigens, also termed neoantigens are a series of immunogenic peptides derived from tumor-specific mutations, instead of from the normal human genome. Many efforts are currently focused on the development of neoantigen-based cancer vaccines for wide medical applications.

Preclinical and clinical studies demonstrate that neoantigens are important targets and could be recognized as non-self by the host immune system. The immunogenicity of neoantigens leading to T cell response has long been demonstrated in humans and identified as the target of adoptive T cell therapies, and can be effectively targeted with personalized vaccines. Improvement in our understanding of oncology and tumor immunology, and elucidation of the immune suppression and escape mechanisms of tumor tissue will expand the application of personalized cancer neoantigen vaccine in the future.

Keywords: Tumor antigen, Vaccination, Immunity, Cancer, T-cell

References:

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2.      The Changing Landscape of Therapeutic Cancer Vaccines—Novel Platforms and Neoantigen Identification; Jessica Jou, Kevin J. Harrington, Mai-Britt Zocca, Eva Ehrnrooth and Ezra E.W. Cohen; DOI: 10.1158/1078-0432.CCR-20-0245 Published February 2021.

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4.      Cell-free tumor antigen peptide-based cancer vaccines; Walter Schmidt,* Michael Buschle,* Wolfgang Zauner,† Helen Kirlappos,* Karl Mechtler,* Barbara Trska,* and Max L. Birnstiel*