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 ϑI1 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 ϑI1 for targeted chemotherapy in a clinically relevant syngeneic metastasis model.
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.