Identifying neoantigens for use in immunotherapy

• Published in: Mammalian genome Vol. 29; no. 11-12; pp. 714 - 730
• Main Authors: Hutchison, Sharon, Pritchard, Antonia L.
• Format: Journal Article
• Language: English
• Published: New York Springer US 01-12-2018; Springer Nature B.V
• Subjects: Algorithms; Animal Genetics and Genomics; Antigens; Autoantigens; Biomedical and Life Sciences; Cancer; Cell Biology; Epitopes; Genomes; Human Genetics; Immune response; Immunogenicity; Immunotherapy; Life Sciences; Mutation; Neoantigens; Proteasomes; Proteins; Tumors; Transporter Associated With Antigen Processing (TAP); Neoantigen Prediction; Epitope Prediction; Binding Groove; Peptide Binding
• ISSN: 0938-8990; 1432-1777
• DOI: 10.1007/s00335-018-9771-6

This review focuses on the types of cancer antigens that can be recognised by the immune system and form due to alterations in the cancer genome, including cancer testis, overexpressed and neoantigens. Specifically, neoantigens can form when cancer cell-specific mutations occur that result in alterations of the protein from ‘self’. This type of antigen can result in an immune response sufficient to clear tumour cells when activated. Furthermore, studies have reported that the likelihood of successful immunotherapeutic targeting of cancer by many different methods was reliant on immune response to neoantigens. The recent resurgence of interest in the immune response to tumour cells, in conjunction with technological advances, has resulted in a large increase in the predicted, identified and functionally confirmed neoantigens. This growth in identified neoantigen sequences has increased the contents of training sets for algorithms, which in turn improves the prediction of which genetic mutations may form neoantigens. Additionally, algorithms predicting how proteins will be processed into peptide epitopes by the proteasome and which peptides bind to the transporter complex are also improving with this research. Now that large screens of all the tumour-specific protein altering mutations are possible, the emerging data from assessment of the immunogenicity of neoantigens suggest that only a minority of variants will form targetable epitopes. The potential for immunotherapeutic targeting of neoantigens will therefore be greater in cancers with a higher frequency of protein altering somatic variants. There is considerable potential in the use of neoantigens to treat patients, either alone or in combination with other immunotherapies and with continued advancements, these potentials will be realised.