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Targeted Therapy with a Novel Enediyene Antibiotic Calicheamicin ^I₁ Effectively Suppresses Growth and Dissemination of Liver Metastases in a Syngeneic Model of Murine Neuroblastoma¹

Departments of Immunology [H. N. L., R. A. R.] and Chemistry [K. C. N.], The Scripps Research Institute, La Jolla, California 92037; Department of Pediatric Hematology/Oncology, University of Tübingen, 72070 Tübingen, Germany [R. H.]; and Department of Pediatric Molecular Biology, Charité-Humboldt University of Berlin, 10117 Berlin, Germany [G. G., W. W.]

The suppression of metastases in malignant diseases is one of the major goals in targeted chemotherapy. This was achieved with an antibody drug conjugate between a novel, rationally designed enediyene antibiotic calicheamicin ^I₁ of exceptionally high cytotoxic potency and an antiganglioside GD₂ monoclonal antibody 14G2a. Effective suppression of hepatic metastases was demonstrated in a novel syngeneic model of murine neuroblastoma that simulates the situation in patients in terms of antigen heterogeneity and presence of the target antigen on normal tissues. Here, we describe the first successful use of calicheamicin ^I₁ for targeted chemotherapy in a clinically relevant syngeneic metastasis model.

¹ This work was supported by NIH Outstanding Investigator's Award CA 42508 (to R. A. R.) and by the Madeleine-Bühler-Stiftung, Germany (to W. W.). H. N. L. was supported by a training grant from the Deutsche Forschungsgemeinschaft. This is The Scripps Research Institute's manuscript no. 11620-IMM.

² To whom requests for reprints should be addressed, at Department of Immunology. The Scripps Research Institute, 10550 North Torrey Pines Road, IMM 13, La Jolla, CA 92037.

Received 5/11/98. Accepted 5/29/98.

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