title: Feasibility analysis of p62 (SQSTM1)-encoding DNA vaccine as a novel cancer immunotherapy.
abstract: 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.
authors.affiliation: CureLab Oncology Inc , Newton, MA, USA.
authors.forename: Vladimir L
authors.initials: VL
authors.lastname: Gabai
authors.forename: Victor I
authors.initials: VI
authors.lastname: Shifrin
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D000951:Antigens, Neoplasm / Q000235:genetics / Q000378:metabolism*; D001343:Autophagy; D019496:Cancer Vaccines; D004285:Dogs; D006801:Humans; D007167:Immunotherapy; D051379:Mice; D009369:Neoplasms / Q000276:immunology / Q000628:therapy*; D051381:Rats; D000071456:Sequestosome-1 Protein; D015398:Signal Transduction; D019444:Vaccines, DNA; D023041:Xenograft Model Antitumor Assays
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D000951:Antigens, Neoplasm; D019496:Cancer Vaccines; C099718:SQSTM1 protein, human; D000071456:Sequestosome-1 Protein; D019444:Vaccines, DNA
keywords: Autophagy; cancer vaccine; transformation; tumor antigen