Antitumor effect of VEGF neutralizing antibody on gastrointestinal carcinoma.

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Four human carcinoma xenografts, two human colon carcinomas and two gastric carcinomas, were transplanted orthotopically into nude mice : Northern blot analysis demonstrated the expression of VEGF mRNA in all 4 xenografts and VEGF protein was also demonstrated to be produced from all of them by ELISA.The VEGF neurtralizing antibody or same volume of saline was administered intraperitoneally on alternative days from day 10 after transplantation. With each of the four xenografts, administration of antibody significantly inhibited not only primary tumor growth but also macroscopic liver metastasis, although the growth rate varied among the 4 cancer xenografts. 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 potent target for cancer therapy. The excellent therapeutic effect of netralizing antibody was also demonstrated against endocrine neoplasm derived from duodenum.The mechanism of the effect of neutralizing antibody was also investigated. The inhibition of angiogenesis by neutralizing antibody which was shown quntitatively by immunohistochemistry followed by the apoptosis of tumor cells was mainly contributed to its inhibitory effect on tumor growth and metastasis.