Conjugates of mitomycin C with the immunoglobulin M monomer fragment of a monoclonal anti-MM46 immunoglobulin M antibody with or without serum albumin as intermediary.
In studies on antitumor antibody-drug conjugates as potential antitumor agents with improved tumor specificity, conjugates of mitomycin C (MMC) with the IgMs fragment of a monoclonal IgM antibody to a tumor-associated antigen (MM antigen) on mouse mammary tumor MM46 cell (anti-MM46 IgMs) were prepared by direct and bovine serum albumin (BSA)-mediated indirect conjugation. MMC was linked to the IgMs and BSA by the use of 1a-[4-(N-succinimidoxycarbonyl)butyryl]mitomycin C, which allowed the slow release of MMC. In the indirect conjugation, the thiol group of BSA was first protected as the 2-pyridyldithio group and, after the MMC binding, regenerated with dithiothreitol, and the resulting BSA-MMC was reacted with the IgMs having the maleimide group introduced with N-succinimidyl m-(N-maleimido)benzoate. Anti-MM46 IgMs-MMC was more cytotoxic against the target MM antigen-positive but Thy 1.2 antigen-negative MM46 cells than control anti-Thy 1.2 IgM-MMC. No such selective cytotoxicity was observed between anti-MM46 IgMs-MMC and anti-Thy 1.2 IgMs-MMC against the MM antigen- and Thy 1.2 antigen-negative MM48 cells. Anti-MM46 IgMs-BSA-MMC was more cytotoxic against MM46 cells than was a mixture of unconjugated anti-MM46 IgMs and BSA-MMC.
D000818:Animals; D000903:Antibiotics, Antineoplastic; D000911:Antibodies, Monoclonal / Q000138:chemical synthesis* / Q000633:toxicity; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D007128:Immunoglobulin Fragments; D007075:Immunoglobulin M; D000922:Immunotoxins; D008325:Mammary Neoplasms, Experimental / Q000473:pathology; D051379:Mice; D008809:Mice, Inbred C3H; D016685:Mitomycin; D008937:Mitomycins / Q000138:chemical synthesis* / Q000633:toxicity; D012710:Serum Albumin, Bovine; D013439:Sulfhydryl Reagents
D000903:Antibiotics, Antineoplastic; D000911:Antibodies, Monoclonal; D007128:Immunoglobulin Fragments; D007075:Immunoglobulin M; D000922:Immunotoxins; D008937:Mitomycins; D013439:Sulfhydryl Reagents; C046104:mitomycin C-immunoglobulin M antibody conjugate; D012710:Serum Albumin, Bovine; D016685:Mitomycin