Immunochemotherapy of a murine thymoma with the use of idarubicin monoclonal antibody conjugates.
Idarubicin is a derivative of daunomycin and is characterized by the absence of the methoxyl group at the C-4 position. It has been reported to have greater therapeutic effect than daunomycin. Idarubicin was chemically coupled to a monoclonal antibody to the murine Ly-2.1 alloantigen and the cytotoxicity of the drug-monoclonal antibody conjugate versus free idarubicin was tested in vitro against Ly-2+ and Ly-2- tumor cell lines. Some loss of idarubicin activity occurred upon conjugation to the monoclonal antibody; however, antibody activity was preserved and selective cytotoxicity for the Ly-2+ cell line was observed. By contrast free idarubicin was equally cytotoxic for all cell lines (Ly-2+ and Ly-2-). Idarubicin-anti-Ly-2.1 conjugates were tested for their capacity to inhibit solid tumor growth in (Ly-2.1-, Ly-2.2+) (C57BL/6 x BALB/c)F1 mice while their nonspecific effects were monitored by histological examination. The idarubicin-anti-Ly-2.1 conjugates when injected i.v. or directly into the tumor were observed to inhibit tumor growth more effectively than idarubicin or anti-Ly-2.1 alone, with smaller tumors being completely eradicated within several days of the completion of treatment.
Department of Pathology, University of Melbourne, Parkville, Victoria, Australia.
G A
GA
Pietersz
M J
MJ
Smyth
I F
IF
McKenzie
D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000627:therapeutic use*; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D003630:Daunorubicin / Q000031:analogs & derivatives* / Q000627:therapeutic use; D006801:Humans; D015255:Idarubicin; D007167:Immunotherapy; D051379:Mice; D008815:Mice, Inbred Strains; D013945:Thymoma / Q000188:drug therapy / Q000276:immunology / Q000628:therapy*; D013953:Thymus Neoplasms / Q000188:drug therapy / Q000276:immunology / Q000628:therapy*
D000903:Antibiotics, Antineoplastic; D000911:Antibodies, Monoclonal; D015255:Idarubicin; D003630:Daunorubicin