The demonstration that for infectious diseases vaccine-induced immunity is in principle only effective before rather than after infection occurs, provides valuable insights in understanding the nature of immune system and the challenges in cancer treatment. Besides the already known underlying counter-back mechanisms, the astronomical numbers of tumor cells in established tumors could overwhelm the limited amount of specific T cells induced by vaccination, which may account for the modest efficiency of immunotherapy against cancer. We speculate that the long window period for cancer development will allow immune-intervening strategies (e.g., the proper prophylactic vaccination) to promote adaptive mechanisms toward an enhanced immunosurveillance, which could effectively eradicate or at least control the few precancerous cells undergoing neoplastic transformation during early premalignant stages in cancer development, and protect the host from lethal tumor formation. It should be emphasized that the pre-cancer-associated antigens but not the tumor-associated antigens seem to be the suitable antigens for designing prophylactic cancer vaccines. In addition, an ideal prophylactic cancer vaccine may contain multiple pre-cancer-associated antigens, which will provide broad and effective immune protection in a heterogeneous human population. Finally, we demonstrated that placenta-derived gp96, which can be readily obtained in high amount for vaccination, has the ability to initiate antitumor T-cell immunity via association with multiple embryo-cancer antigens. Further understanding placental gp96 associated with carcinoembryonic antigen repertoires that orchestrate immune defense networks against cancer formation will allow to provide an effective prophylactic approach in cancer prevention.
