Vaccination with viable human umbilical vein endothelial cells prevents metastatic tumors by attack on tumor vasculature with both cellular and humoral immunity.
OBJECTIVE
Because tumor endothelium is rarely targeted by immunity but is critically important for tumor growth, the immunity against tumor endothelium is to be developed as a novel antitumor strategy.


METHODS
First, viable human umbilical vein endothelial cells (HUVEC) were immunized to C57BL/6 and BALB/c mice to evoke specific CTLs as well as antibodies against tumor endothelium. Lewis lung carcinoma or myeloma cells were subsequently inoculated to evaluate the effect on tumor growth by vaccination. Second, the effect on tumor metastasis by vaccination was studied using tumor-resected mice receiving HUVEC immunization 3 days after excision. Third, the immune sera and T lymphocytes from HUVEC-immunized mice were transferred to tumor-bearing mice and added to cultured HUVECs to investigate their antiproliferative effect.


RESULTS
Viable HUVEC immunization showed potent antitumor effects in Lewis lung carcinoma and myeloma tumor models. Both immune sera and CTL inhibited tumor growth and specifically suppressed proliferation of HUVECs. Particularly, tumors entirely disappeared on day 90 after tumor inoculation in four of six tumor-bearing mice receiving CTL therapy. In a metastatic tumor model, we found that the HUVEC vaccination prolonged life span from 30.9 to 41.5 days after tumor resection compared with PBS-treated mice without apparent side effects.


CONCLUSIONS
Vaccination with viable HUVECs evoked both humoral and cellular immunity against tumor microvasculature, and therefore significantly inhibited tumor growth and prolonged life span of tumor-resected mice. This may provide with a novel treatment for metastatic tumors. Moreover, we have established a convenient method to evoke specific CTL against tumor angiogenesis.
Chen
Xin-Yuan
XY
Institute of Molecular Medicine and State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, 22 Hankou Road, Nanjing 210093, China.
Zhang
Wei
W
Zhang
Wang
W
Wu
Sheng
S
Bi
Feng
F
Su
Yi-Jing
YJ
Tan
Xiang-Yang
XY
Liu
Jian-Ning
JN
Zhang
Jing
J
D000818:Animals; D000917:Antibody Formation; D018931:Antineoplastic Agents, Hormonal / Q000494:pharmacology; D018827:Carcinoma, Lewis Lung / Q000098:blood supply / Q000276:immunology / Q000517:prevention & control*; D004730:Endothelium, Vascular / Q000276:immunology*; D006801:Humans; D007111:Immunity, Cellular; D008175:Lung Neoplasms / Q000098:blood supply / Q000276:immunology / Q000517:prevention & control*; D008297:Male; D008546:Melanoma, Experimental / Q000098:blood supply / Q000276:immunology / Q000517:prevention & control*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008819:Mice, Nude; D009362:Neoplasm Metastasis; D009389:Neovascularization, Pathologic / Q000276:immunology*; D015996:Survival Rate; D013601:T-Lymphocytes / Q000276:immunology; D014471:Umbilical Veins / Q000166:cytology; D014611:Vaccination; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
D018931:Antineoplastic Agents, Hormonal; D042461:Vascular Endothelial Growth Factor A