Active immunotherapy of tumors with a recombinant xenogeneic endoglin as a model antigen.
Angiogenesis play a critical role in tumor growth and metastasis. Increasing evidence suggests that endoglin is a powerful marker of angiogenesis in solid malignancies. Thus, breaking of immune tolerance of self-endoglin-associated angiogenesis is an attractive approach to cancer therapy. To test this concept, we recombined the extracellular domains of porcine endoglin, and used it as a xenogeneic vaccine. We found that immunotherapy with porcine endoglin was effective at both protective and therapeutic anti-tumor immunity in several mouse tumor models. Autoantibodies against mouse endoglin were identified by Western blot and ELISA. IgG1 and IgG2b were substantially increased. Anti-endoglin antibody-producing B cells were detectable by ELISPOT assay. There was endothelial deposition of immunoglobulins within tumors. The anti-tumor activity was also induced by the adoptive transfer of the purified immunoglobulins. Angiogenesis was apparently inhibited within the tumor tissues and on the alginate beads. The increased apoptotic cells were found within the tumor tissues from the mice treated with porcine endoglin. The anti-tumor activity and production of autoantibodies against mouse endoglin could be abrogated by depletion of CD4(+) T lymphocytes. Remarkably, no marked toxicity was found in the immunized mice. These observations may provide an alternative rational strategy for active cancer immunotherapy.
Tan
Guang-Hong
GH
Key Laboratory of Biotherapy of Human Diseases, Ministry of Education, P R China.
Wei
Yu-Quan
YQ
Tian
Ling
L
Zhao
Xia
X
Yang
Li
L
Li
Jiong
J
He
Qiu-Ming
QM
Wu
Yang
Y
Wen
Yan-Jun
YJ
Yi
Tao
T
Ding
Zhen-Yu
ZY
Kan
Bin
B
Mao
Yong-Qiu
YQ
Deng
Hong-Xin
HX
Li
Hong-Li
HL
Zhou
Chun-Hua
CH
Fu
Chun-Hua
CH
Xiao
Fei
F
Zhang
Xiao-Wei
XW
D019264:Adoptive Transfer; D000818:Animals; D015703:Antigens, CD; D015478:Antigens, Heterophile / Q000737:chemistry / Q000276:immunology*; D017209:Apoptosis; D001323:Autoantibodies / Q000276:immunology; D014408:Biomarkers, Tumor / Q000737:chemistry / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D019496:Cancer Vaccines / Q000276:immunology*; D018827:Carcinoma, Lewis Lung / Q000098:blood supply / Q000276:immunology / Q000473:pathology; D000071063:Endoglin; D007108:Immune Tolerance / Q000276:immunology; D008546:Melanoma, Experimental / Q000276:immunology / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D009369:Neoplasms / Q000098:blood supply / Q000276:immunology* / Q000473:pathology / Q000628:therapy*; D009389:Neovascularization, Pathologic; D017434:Protein Structure, Tertiary; D011956:Receptors, Cell Surface; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000276:immunology*; D013552:Swine / Q000276:immunology; D014611:Vaccination; D019010:Vascular Cell Adhesion Molecule-1 / Q000737:chemistry / Q000276:immunology*
D015703:Antigens, CD; D015478:Antigens, Heterophile; D001323:Autoantibodies; D014408:Biomarkers, Tumor; D019496:Cancer Vaccines; C064206:ENG protein, human; D000071063:Endoglin; D011956:Receptors, Cell Surface; D011993:Recombinant Fusion Proteins; D019010:Vascular Cell Adhesion Molecule-1