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Immunochemotherapy of a Murine Thymoma with the Use of Idarubicin Monoclonal Antibody Conjugates

Research Centre for Cancer and Transplantation, Department of Pathology, The University of Melbourne, Parkville, Victoria, 3052, Australia

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.

¹ To whom requests for reprints should be addressed.

Received 8/ 5/87. Revised 11/10/87. Accepted 11/17/87.