title: Enhanced antitumor efficacy by combination treatment with a human umbilical vein endothelial cell vaccine and a tumor cell lysate-based vaccine.
abstract: Angiogenesis inhibitors combined with other anticancer drugs have been shown to inhibit tumor growth in animal models and some of them were recently used in clinical trials. In the present study, a whole hepatocellular carcinoma cell lysate based vaccine with diphtheria toxin (DT) and two tandem repeats of microbial HSP70 peptide epitope 407-426 (2 mHSP70407-426, M2) as adjuvant, which was called HDM, was combined with a whole human umbilical vein endothelial cell (HUVEC) vaccine to develop a combination treatment regimen. This combination treatment regimen was named HUVEC-HDM, which was supposed to enhance its antitumor efficiency. HUVEC-HDM was administrated subcutaneously in both prophylactic and therapeutic procedures. Compared to either single vaccine, HUVEC-HDM induced a more significant inhibition on the growth and metastasis of H22 hepatocellular carcinoma in mice and prolonged the survival of tumor-bearing mice. Besides, HUVEC-HDM immunization elicited strong humoral and cellular immune responses targeting tumor cell as well as tumor angiogenesis, which could be responsible for the enhanced antitumor effect. Moreover, histochemistry analysis showed that HUVEC-HDM induced large areas of continuous necrosis within tumors, correlating well with the extent of tumor inhibition. These results not only highlight the superiority of the combined HUVEC-HDM treatment regimen, but also support the translation of such approaches into the clinic for the treatment of patients with hepatocellular carcinoma.
authors.affiliation: State Key Laboratory of Natural Medicines, China Pharmaceutical University, 24 Tongjia Xiang, Nanjing, 210009, People's Republic of China, xumaolei1234@163.com.
authors.forename: Maolei
authors.initials: M
authors.lastname: Xu
authors.forename: Ling
authors.initials: L
authors.lastname: Zhou
authors.forename: Peng
authors.initials: P
authors.lastname: Zhang
authors.forename: Yong
authors.initials: Y
authors.lastname: Lu
authors.forename: Chiyu
authors.initials: C
authors.lastname: Ge
authors.forename: Wenjun
authors.initials: W
authors.lastname: Yao
authors.forename: Yun
authors.initials: Y
authors.lastname: Xing
authors.forename: Wen
authors.initials: W
authors.lastname: Xiao
authors.forename: Yuankai
authors.initials: Y
authors.lastname: Dong
authors.forename: Jie
authors.initials: J
authors.lastname: Wu
authors.forename: Rongyue
authors.initials: R
authors.lastname: Cao
authors.forename: Taiming
authors.initials: T
authors.lastname: Li
mesh_terms: D000818:Animals; D000912:Antibodies, Neoplasm / Q000097:blood; D019496:Cancer Vaccines; D006528:Carcinoma, Hepatocellular / Q000098:blood supply / Q000473:pathology / Q000628:therapy*; D002457:Cell Extracts / Q000276:immunology; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D003602:Cytotoxicity, Immunologic; D061307:Human Umbilical Vein Endothelial Cells / Q000276:immunology / Q000378:metabolism / Q000637:transplantation*; D006801:Humans; D007111:Immunity, Cellular; D056724:Immunity, Humoral; D008114:Liver Neoplasms, Experimental / Q000098:blood supply / Q000473:pathology / Q000628:therapy*; D008175:Lung Neoplasms / Q000098:blood supply / Q000556:secondary / Q000628:therapy*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D009389:Neovascularization, Pathologic / Q000517:prevention & control; D013602:T-Lymphocytes, Cytotoxic / Q000502:physiology
chemical_list: D000912:Antibodies, Neoplasm; D019496:Cancer Vaccines; D002457:Cell Extracts