Combination of low-dose cisplatin and recombinant xenogeneic endoglin as a vaccine induces synergistic antitumor activities.
Angiogenesis is critical to the growth and metastasis of solid tumors, and acquired drug resistance is one of the major hindrances to chemotherapy. Thus, we sought a rational strategy using the combination of antiangiogenic biotherapy and chemotherapy for cancer therapy. We explored the efficacy of a strategy combining low-dose cisplatin and a recombinant xenogeneic endoglin as a protein vaccine, which we previously demonstrated to have effective antiangiogenic effects in several mouse models. We found that both low-dosage cisplatin and xenogeneic endoglin vaccine individually resulted in effective suppression of tumor growth in 2 tumor models via inhibition of tumor angiogenesis. Remarkably, the combination therapy resulted in not only significant antiangiogenic effects but also additional promotion of tumor cell apoptosis and inhibition of tumor cell proliferation, without any ensuing increase in host toxicity during the course of treatment, which lasted for 6 months. In addition, the combination demonstrated a synergistic relationship, which was shown in all of the synergistic indexes, i.e., tumor volume, angiogenesis, apoptosis and proliferation. Both antibodies and antibody-producing B cells against mouse self-endoglin were observed in all mice immunized by the xenogeneic endoglin vaccine (alone and combination), which suggested that low-dose cisplatin did not suppress the host immune response but potentiated the antitumor activity of the xenogeneic endoglin vaccine. These observations may provide the basis for an effective alternative strategy for cancer therapy in the near future.
Tan
Guang-Hong
GH
Key Laboratory of Biotherapy of Human Diseases of the Ministry of Education and Cancer Center, West China Hospital, West China Medical School, Sichuan University, Chengdu, People's Republic of China.
Tian
Ling
L
Wei
Yu-Quan
YQ
Zhao
Xia
X
Li
Jiong
J
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
Zou
Chun-Hua
CH
Fu
Chun-Hua
CH
D000818:Animals; D015703:Antigens, CD; D015478:Antigens, Heterophile / Q000008:administration & dosage / Q000276:immunology / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000276:immunology / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects; D019496:Cancer Vaccines / Q000276:immunology*; D018827:Carcinoma, Lewis Lung / Q000188:drug therapy*; D002945:Cisplatin / Q000008:administration & dosage / Q000276:immunology / Q000627:therapeutic use*; D003110:Colonic Neoplasms / Q000188:drug therapy*; D003131:Combined Modality Therapy; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D000071063:Endoglin; D005260:Female; D006801:Humans; D051379:Mice; D009389:Neovascularization, Pathologic; D011956:Receptors, Cell Surface; D014183:Transplantation, Heterologous; D019010:Vascular Cell Adhesion Molecule-1 / Q000008:administration & dosage / Q000276:immunology / Q000627:therapeutic use*
D015703:Antigens, CD; D015478:Antigens, Heterophile; D000970:Antineoplastic Agents; D019496:Cancer Vaccines; C064206:ENG protein, human; D000071063:Endoglin; D011956:Receptors, Cell Surface; D019010:Vascular Cell Adhesion Molecule-1; D002945:Cisplatin