Abstract
Unlike traditional cancer therapies, cancer vaccines (CVs) harness a high specificity of the host’s immunity to kill tumor cells. CVs can train and bolster the patient’s immune system to recognize and eliminate malignant cells by enhancing immune cells’ identification of antigens expressed on cancer cells. Various features of antigens like immunogenicity and avidity influence the efficacy of CVs. Therefore, the choice and application of antigens play a critical role in establishing and developing CVs. Tumor-associated antigens (TAAs), a group of proteins expressed at elevated levels in tumor cells but lower levels in healthy normal cells, have been well-studied and developed in CVs. However, immunological tolerance, HLA restriction, and adverse events are major obstacles that threaten TAA-based CVs’ efficacy due to the “self-protein” characteristic of TAAs. As “abnormal proteins” that are completely absent from normal cells, tumor-specific antigens (TSAs) can trigger a robust immune response against tumor cells with high specificity and without going through central tolerance, contributing to cancer vaccine development feasibility. In this review, we focus on the unique features of TAAs and TSAs and their application in vaccines, summarizing their performance in preclinical and clinical trials.
Highlights
Since tumor antigens’ discovery, the expression pattern of which was different from normal tissues, it became obvious that tumors are immunologically distinguished from other tissues
It has turned out that most initially described human tumor antigens are not specific for tumors; they were designated as tumor-associated antigens (TAAs) and nowadays generally accepted as less suitable for being immunogens in anticancer vaccines
cancer-germline antigens (CGAs) are expressed in testis barrier and devoid expression of HLA class I molecules on the surface of germ cells, various kinds of cancer ectopically, mainly due to epigenetic regulation activities, includCGAs are capable of avoiding interaction and recognition by the immune system when ing DNA
Summary
Since tumor antigens’ discovery, the expression pattern of which was different from normal tissues, it became obvious that tumors are immunologically distinguished from other tissues. It has turned out that most initially described human tumor antigens are not specific for tumors; they were designated as tumor-associated antigens (TAAs) and nowadays generally accepted as less suitable for being immunogens in anticancer vaccines. Proteins from other immuneprivileged tissues were found to be expressed in tumors, such as neuronal tissue and retina They were designated as onconeural and cancer-retina antigens, respectively. Acknowledging that such antigens can be expressed in tumors, but they are not fully tumor-specific due to their normal immune-privileged expression, they can be grouped as immune-privileged antigens. The intensity of the mutagenic process is different in different malignancies Such a tumor feature was designated as a tumor mutation burden (TMB). We discuss prospective tumor antigens, tumorspecific and immune-privileged antigens, that are worth using as anticancer vaccine components. Regarding the upcoming era of a personalized approach in medicine, a hypothetic pipeline of how to choose antigens for individual cancer treatment or preventive vaccination is discussed
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