Post-Translational Modifications in Tumor-Associated Antigens as a Platform for Novel Immuno-Oncology Therapies

SIMPLE SUMMARY: Tumor-associated antigens (TAAs) are antigens present in tumor cells, but are also expressed in normal cells. However, TAAs are aberrantly expressed by tumor cells, and can elicit multiple specific immune responses. One key feature of TAAs is the presence of post-translational modifications often absent in normal proteins. This article offers an overview of the role of post-translational modifications in TAAs in eliciting a specific immune response, which makes them targets for immuno-oncology therapy. Both preclinical and clinical studies will be discussed. ABSTRACT: Post-translational modifications (PTMs) are generated by adding small chemical groups to amino acid residues after the translation of proteins. Many PTMs have been reported to correlate with tumor progression, growth, and survival by modifying the normal functions of the protein in tumor cells. PTMs can also elicit humoral and cellular immune responses, making them attractive targets for cancer immunotherapy. This review will discuss how the acetylation, citrullination, and phosphorylation of proteins expressed by tumor cells render the corresponding tumor-associated antigen more antigenic and affect the immune response in multiple cancers. In addition, the role of glycosylated protein mucins in anti-cancer immunotherapy will be considered. Mucin peptides in combination with stimulating adjuvants have, in fact, been utilized to produce anti-tumor antibodies and vaccines. Finally, we will also outline the results of the clinical trial exploiting glycosylated-MUC1 as a vaccine in different cancers. Overall, PTMs in TAAs could be considered in future therapies to result in lasting anti-tumor responses.