Production of a macromomycin (MCR)-monoclonal antibody conjugate and its biological activity.
Macromomycin (MCR), an unique membrane-reactive anticancer antibiotic, was incubated with murine monoclonal anti-HLA IgG1 antibody (H-1) in the presence of carbodiimide. The resulting mixture was fractionated with a Sephadex G-200 column. The first and second fractions were shown to contain MCR-(H-1) conjugate by the elution profile, as well as by the Sarcina lutea growth inhibition assay and Ouchterlony double-diffusion method. A membrane immunofluorescence test with anti-MCR and anti-mouse IgG antibodies demonstrated specific localization of MCR-(H-1) on the surface of HLA-bearing NALL -1 cells. MCR-(H-1) inhibited the growth of HLA-lacking NS-1 cells statistically less effectively than MCR alone (p less than 0.01). On the other hand, the conjugate and free MCR equally inhibited the growth and 3H-TdR incorporation of HLA-bearing NALL -1 cells. These results indicate that the antibody-bound MCR retained both MCR and antibody activities, and thus exerted antibody-targeting MCR cytotoxicity in vitro.
D000900:Anti-Bacterial Agents; D000911:Antibodies, Monoclonal / Q000276:immunology*; D002460:Cell Line; D002462:Cell Membrane; D006680:HLA Antigens / Q000276:immunology*; D006801:Humans; D006825:Hybridomas / Q000276:immunology; D007074:Immunoglobulin G / Q000276:immunology*; D007158:Immunologic Techniques; D010455:Peptides / Q000276:immunology
D000900:Anti-Bacterial Agents; D000911:Antibodies, Monoclonal; D006680:HLA Antigens; D007074:Immunoglobulin G; D010455:Peptides; C001666:auromomycin