Nonviral Oncogenic Antigens and the Inflammatory Signals Driving Early Cancer Development as Targets for Cancer Immunoprevention

摘要

Cancer immunoprevention is an emerging field that holds much promise. Within the last 20 years, prophylactic vaccines have been implemented on the population level for the immunoprevention of carcinomas induced by viruses, specifically hepatitis B virus (HBV) and human papillomavirus (HPV) infection. Armed with the success of prophylactic vaccines that prevent viral induced tumors, the field must overcome its next hurdle: to develop robust prophylactic vaccines that prevent the remaining >80% of human cancers not induced by viral infection. In this review, we discuss some of the most promising non-virus associated prophylactic vaccines that target endogenous neo-antigens including the earliest oncogene products, altered mucin 1 (MUC1) and α-enolase (ENO1), all of which produce new targets in the earliest stages of non-viral induced tumorigenesis. We also highlight a novel attenuated Listeria monocytogenes-based vaccine expressing mutant oncogene Kras^G12D (LM-Kras) effective in a pancreatic cancer model. A novel chimeric human/rat HER-2 plasmid vaccine (HuRT-DNA vaccine) effective in a breast cancer model is also discussed. In addition to prophylactic vaccine developments, this review highlights the potential use of classic drugs like aspirin and metformin as chemopreventive agents that can potentially be used as adjuvants to enhance the anti-cancer immunogenicity and efficacy of non-infectious prophylactic vaccines by modulating the inflammatory pathways within the early tumor microenvironment (TME) that propels tumorigenesis. Finally, timing of prophylactic vaccine administration is critical to its immunopreventive efficacy, providing a necessary role of current and emerging biomarkers for cancer screening and early cancer detection.