Feasibility analysis of p62 (SQSTM1)-encoding DNA vaccine as a novel cancer immunotherapy.
Cancer immunotherapy is a thriving field, but its clinical achievements are modest so far. One of its major hurdles seems to be finding a feasible cancer antigen as a target for immune response. After many years of research, three major criteria for choice of tumor antigens emerged. An antigen should be: (i) immunogenic; (ii) essential for cancers cells (to avoid its loss through immunoediting), but dispensable for normal tissues to reduce the risk of toxicity, and (iii) overexpressed in tumors as compared to the normal tissues. Here we argue that p62 (SQSTM1), a protein involved in autophagy and signal transduction, fits all the above criteria and can be chosen as a novel cancer antigen. Accordingly, we carried out an extensive study and found antitumor and antimetastatic activity of p62-encoding DNA vaccine in five types of commonly used transplantable tumor models of mice and rats, and spontaneous tumors in several dogs. Given that toxicity of p62 vaccine was minimal, if any, we believe that p62-encoding vaccine merits further clinical development.
['Gabai|Vladimir L|VL|', 'Shifrin|Victor I|VI|']
D048868:Adaptor Proteins, Signal Transducing D000818:Animals D000951:Antigens, Neoplasm D001343:Autophagy D019496:Cancer Vaccines D004285:Dogs D006801:Humans D007167:Immunotherapy D051379:Mice D009369:Neoplasms D051381:Rats D000071456:Sequestosome-1 Protein D015398:Signal Transduction D019444:Vaccines, DNA D023041:Xenograft Model Antitumor Assays
tumor antigen Autophagy cancer vaccine transformation