Anti-tumor and anti-metastatic effects of human-vascular-endothelial-growth-factor-neutralizing antibody on human colon and gastric carcinoma xenotransplanted orthotopically into nude mice.
In order to determine whether the inhibition of vascular-endothelial-growth-factor (VEGF) activity by administration of an immunoneutralizing antibody could suppress tumor growth and metastasis in spontaneous metastatic models of human colon and gastric carcinoma, 4 human carcinoma xenografts, 2 human colon carcinomas (TK4 and TK 13) and 2 gastric carcinomas (MT2 and MT5) were transplanted orthotopically into nude mice. The anti-VEGF antibody (MV833, 100 microg/mouse) or the same volume of saline was administered i.p. on alternative days from day 10 after transplantation. With each of the 4 xenografts, administration of MV833 significantly inhibited not only primary tumor growth but also macroscopic liver metastasis, although the growth rate varied. The inhibitory effect of MV833 on primary tumor growth appeared to have no correlation with the level of VEGF in tumor. Body-weight gain in each treated group was comparable with that in the control group. No toxicity of the antibody was observed. These results suggest that an anti-VEGF antibody can be effective against a wide variety of cancers, and that VEGF may be a possible target for cancer therapy.
Kanai
T
T
Second Department of Surgery, Hamamatsu University School of Medicine, Japan.
Konno
H
H
Tanaka
T
T
Baba
M
M
Matsumoto
K
K
Nakamura
S
S
Yukita
A
A
Asano
M
M
Suzuki
H
H
Baba
S
S
D000230:Adenocarcinoma / Q000188:drug therapy*; D000818:Animals; D000906:Antibodies / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D003110:Colonic Neoplasms / Q000188:drug therapy*; D016228:Endothelial Growth Factors / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D008222:Lymphokines / Q000276:immunology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D013274:Stomach Neoplasms / Q000188:drug therapy*; D014183:Transplantation, Heterologous; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
D000906:Antibodies; D000970:Antineoplastic Agents; D016228:Endothelial Growth Factors; D008222:Lymphokines; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors