Prophylactic cancer vaccine, from concept to reality?  

作　　者：Bao Zhao Xin Li Beinan Wang Bin Gao Songdong Meng 

机构地区：[1]Key Laboratory of Pathogenic Microbiology and Immunology,Institute of Microbiology, Chinese Academy of Sciences

出　　处：《Chinese Science Bulletin》2014年第10期944-949,共6页

基　　金：supported by the National Natural Science Foundation of China(31230026,91029724,81021003 and 81102018);Beijing Natural Science Foundation(5112021)

摘　　要：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 tumorassociated 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.The demonstration that for infectious diseasesvaccine-induced immunity is in principle only effectivebefore rather than after infection occurs, provides valuableinsights in understanding the nature of immune system andthe challenges in cancer treatment. Besides the alreadyknown underlying counter-back mechanisms, the astro-nomical numbers of tumor cells in established tumorscould overwhelm the limited amount of specific T cellsinduced by vaccination, which may account for the modestefficiency of immunotherapy against cancer. We speculatethat the long window period for cancer development willallow immune-intervening strategies （e.g., the proper pro-phylactic vaccination） to promote adaptive mechanismstoward an enhanced immunosurveillance, which couldeffectively eradicate or at least control the few precancer-ous cells undergoing neoplastic transformation during earlypremalignant stages in cancer development, and protect thehost from lethal tumor formation. It should be emphasizedthat the pre-cancer-associated antigens but not the tumor-associated antigens seem to be the suitable antigens fordesigning prophylactic cancer vaccines. In addition, anideal prophylactic cancer vaccine may contain multiplepre-cancer-associated antigens, which will provide broadand effective immune protection in a heterogeneous humanpopulation. Finally, we demonstrated that placenta-derivedgp96, which can be readily obtained in high amount forvaccination, has the ability to initiate antitumor T-cellimmunity via association with multiple embryo-cancerantigens. Further understanding placental gp96 associatedwith carcinoembryonic antigen repertoires that orchestrateimmune defense networks against cancer formation willallow to provide an effective prophylactic approach incancer prevention.

关 键 词：PROPHYLACTIC cancer VACCINE GP96 PLACENTA Carcinoembryonic ANTIGENS Multivalentvaccine 

分 类 号：R392[医药卫生—免疫学]