[Antitumor effects of the immunoconjugate composed of lidamycin and monoclonal antibody 3G11].
OBJECTIVE
To study the antitumor effects of an immunoconjugate composed of lidamycin (LDM) and monoclonal antibody 3G11 (3G11-LDM conjugate).


METHODS
3G11-LDM conjugate was prepared by using 2-iminothiolane (2-IT) and m-maleimidobenzoyl-N-hydroxy-succimide ester (MBS) as crosslinkers. The molecular weight of the conjugate was measured on non-reduced SDS-PAGE gel. Immunoreactivity of 3G11-LDM conjugate to type IV collagenase or to hepatoma 22 cells was determined by ELISA. The cytotoxicity of the immunoconjugate to hepatoma 22 cells was examined by MTT assay. Antitumor effects of the 3G11-LDM conjugate in vivo were evaluated using subcutaneously transplanted hepatoma 22 tumor model in mice.


RESULTS
The molecular weight of 3G11-LDM conjugate was approximately 160 kDa. 3G11-LDM conjugate retained part of the immunoreactivity of 3G11 to type IV collagenase and hepatoma 22 cells. As compared with free LDM, 3G11-LDM conjugate showed stronger cytotoxicity to hepatoma 22 cells. When administered intravenously (i.v. x 2 on day 1 and 8), 3G11-LDM conjugate, at doses of 0.05 and 0.10 mg.kg-1, inhibited the growth of hepatoma 22 in mice by 87.8% and 97.2% on day 11, respectively, whereas the unconjugated LDM at 0.05 mg.kg-1 inhibited tumor growth by 67.1%. The median survival times for tumor-bearing mice of untreated control, LDM at 0.05 mg.kg-1, 3G11-LDM at 0.05 mg.kg-1, and 3G11-LDM at 0.10 mg.kg-1 were 34, 41.5, 60.5 and 94 d, respectively. Evidently 3G11-LDM was more effective than free LDM in suppressing tumor growth and prolonging the life span of tumor-bearing mice.


CONCLUSIONS
3G11-LDM conjugate shows much stronger antitumor effects than equivalent dose of free LDM and may have promising therapeutic potential in cancer treatment.
D000617:Aminoglycosides / Q000008:administration & dosage / Q000627:therapeutic use*; D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage / Q000627:therapeutic use*; D000911:Antibodies, Monoclonal / Q000276:immunology; D002455:Cell Division / Q000187:drug effects; D004195:Disease Models, Animal; D053281:Enediynes; D005260:Female; D018796:Immunoconjugates / Q000627:therapeutic use*; D008114:Liver Neoplasms, Experimental / Q000188:drug therapy* / Q000473:pathology; D020778:Matrix Metalloproteinase 2 / Q000276:immunology; D020780:Matrix Metalloproteinase 9 / Q000276:immunology; D051379:Mice; D009368:Neoplasm Transplantation; D011897:Random Allocation; D014407:Tumor Cells, Cultured
D000617:Aminoglycosides; D000903:Antibiotics, Antineoplastic; D000911:Antibodies, Monoclonal; D053281:Enediynes; D018796:Immunoconjugates; C058024:C 1027; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9