Antitumor effect of the novel immunoconjugate composed of pingyangmycin and anti-type IV collagenase monoclonal antibody
Dai, Y.; Liu, X-Jun.; Zhen, Y-Su.
Yao Xue Xue Bao 41(1): 41-46
2006
ISSN/ISBN: 0513-4870 PMID: 16683526 Document Number: 604853
Aim To study the antitumor effect of an immunoconjugate composed of pingyangmycin (PYM) and anti-type IV collagenase monoclonal antibody (mAb) 3G11. Methods 3G11-PLG-PYM immunoconjugate was prepared by linking 2-iminothiolane (2-IT) modified mAb to PYM via N-succinimidyl-3-(2-pyridyldithiol)-propionate (SPDP) derived poly-alpha-L-glutamic acid (PLG) backbone as the intermediate drug carrier. Characterization of the conjugate was performed by SDS-PAGE and spectrophotometry. Immunoreactivity of the conjugate against type IV collagenase was determined by ELISA. The cytotoxicity of the conjugate to hepatoma 22 (H22) and KB cells was examined by MTT assay. Antitumor effect of the conjugate in vivo was evaluated in mice bearing subcutaneously implanted H22 tumor, the candidate drugs were administered intravenously by "q2dx6" regimen. Results The molecular weight of the conjugate was approximately 170 kD. The molecular ratio of 3G11-PLG-PYM was 1:2.4:10. The conjugate retained part of the immunoreactivity of mAb 3G11 against the antigen. The cytotoxicity of the conjugate to H22 and KB cells was moderate comparing with free PYM. In vivo however, free PYM inhibited the growth of H22 by 60.6% on day 22 at the dose of 10 mg . kg(-1), while the equivalent dose of 3G11-PLG-PYM conjugate reached 90.8%. The median survival time of the mice treated with the conjugate was prolonged by 71.7% as compared with that of the untreated group, whereas that of free PYM prolonged only 10.9%. 3G11-PLG-PYM conjugate was notably more effective than free PYM in tumor suppression and life span prolongation. Conclusion 3611-PLG-PYM displayed more marked antitumor efficacy than free PYM in vivo and might be a novel candidate for cancer treatment.