Antitumor activity of anti-type IV collagenase monoclonal antibody and its lidamycin conjugate against colon carcinoma

• Published in: World journal of gastroenterology : WJG Vol. 11; no. 29; pp. 4478 - 4483
• Main Authors: Li, Liang, Huang, Yun-Hong, Li, Yi, Wang, Feng-Qiang, Shang, Bo-Yang, Zhen, Yong-Su
• Format: Journal Article
• Language: English
• Published: United States Baishideng Publishing Group Inc 07.08.2005
• Subjects: Aminoglycosides - pharmacology; Animals; Antibiotics, Antineoplastic - pharmacology; Antibodies, Monoclonal - pharmacology; Breast Neoplasms; Carcinoma, Hepatocellular; Collagen Type IV - immunology; Colonic Neoplasms - drug therapy; Colonic Neoplasms - immunology; Colorectal Cancer; Enediynes; Fibrosarcoma; HT29 Cells; Humans; Immunoconjugates - pharmacology; In Vitro Techniques; IV型胶原酶; Liver Neoplasms; Mice; Mice, Inbred BALB C; 单克隆抗体; 抗癌作用; 结肠癌
• ISSN: 1007-9327; 2219-2840
• DOI: 10.3748/wjg.v11.i29.4478

AIM： Type IV collagenase including MMP-2 and -9 plays an important role in cancer cell invasion and metastasis and is an attractive target for rnAb-directed therapy. The irnrnunoreactivity of rnAb 3G11, a rnAb directed against type Ⅳ collagenase in human colorectal carcinomas, was studied by irnrnuno-histochernical （IHC） staining, rnAb 3G11 was conjugated to an antiturnor antibiotic lidarnycin （LDM）. The antiturnor activity of 3G11-LDM conjugate against colon carcinoma was investigated in mice. METHODS： ELISA, gelatin zyrnography, and Western blot assay were used for the biological characterization of rnAb 3G11. The irnrnunoreactivity of rnAb 3G11 with human colorectal carcinomas was detected by IHC staining. The cytotoxicity of LDM and 3G11-LDM conjugate to human colon carcinoma HT-29 cells was examined by clonogenic assay and MTT assay. The therapeutic effect of conjugate 3G11-LDM was evaluated with colon carcinoma 26 in mice. RESULTS： As shown in ELISA, mAb 3Gll reacted specifically with type IV collagenase, while 3G11-LDM conjugate also recognized specifically its respective antigen. In IHC assay, mAb 3G11 showed positive irnrnunoreactivity in most cases of colorectal carcinoma, and negative irnrnunoreactivity in the adjacent non-malignant tissues. By gelatin zyrnography, the inhibition effect of rnAb 3G11 on the secretion activity of type IV collagenase was proved. In terms of IC50 values in MTT assay, the cytotoxicity of LDM to human colon carcinoma HT-29 cells was 10 000-fold more potent than that of rnitornycin C （MMC） and adriarnycin （ADM）. 3G11- LDM conjugate also displayed extremely potent cytotoxicity to human colon carcinoma HT-29 cells with an IC50 value of 5.6× 10^-19 mol/L. 3G11-LDM conjugate at the doses of 0.05 and 0.1 mg/kg inhibited the growth of colon carcinoma 26 in mice by 70.3 and 81.2%, respectively. CONCLUSION： mAb 3G11 is immunoreactive with human colorectal carcinoma and its conjugate with LDM is highly effective against colon carcinoma in mice.