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Therapeutic Efficacy of Anti-Lewis^y Humanized 3S193 Radioimmunotherapy in a Breast Cancer Model: Enhanced Activity When Combined with Taxol Chemotherapy

Tumour Targeting Program, Ludwig Institute for Cancer Research, Melbourne Branch, Austin and Repatriation Medical Centre, Victoria 3084, Australia [K. C., F-T. L., F. E. S., A. M. S.]; Radioimmune and Inorganic Chemistry Section, Radiation Oncology Branch, NIH, Bethesda, Maryland 20892 [M. W. B.]; and Ludwig Institute for Cancer Research, New York Branch, Memorial Sloan-Kettering Cancer Center, New York, New York 10021 [L. J. O.]

Monoclonal antibody therapy may provide new treatment options in the management of metastatic breast cancer by selectively targeting tumors and producing a therapeutic effect, by delivering radiation or other toxins directly to tumor cells, or by producing an intrinsic immune inflammatory response. The effect of ¹³¹I-labeled humanized anti-Lewis^y monoclonal antibody 3S193 (hu3S193) was compared with that of placebo and radiolabeled huA33 control antibody in a series of radioimmunotherapy experiments in a MCF-7 xenografted BALB/c nude mouse breast cancer model. The maximum tolerated dose of ¹³¹I-labeled antibody occurred at 200 µCi/mouse, at which dose level three of six mice that received ¹³¹I-hu3S193 showed significant tumor growth inhibition in contrast to no responses in the comparable ¹³¹I-huA33 control treatment arm. Breast cancer is an ideal model to test the efficacy of combined modalities given its known sensitivity to both radiotherapy and chemotherapy. The synergy between radioimmunotherapy and chemotherapy was therefore also explored using a combination of ¹³¹I-labeled hu3S193 antibody and Taxol using subtherapeutic doses of each agent. The combination of Taxol and 100 µCi of ¹³¹I-hu3S193 produced significant tumor inhibition in 80% of mice, whereas no responses were seen with either treatment modality alone or the combination of Taxol and ¹³¹I-huA33. These results support a potential therapeutic role of radiolabeled hu3S193 in the treatment of breast cancer, including combination therapy with Taxol, and warrants further investigation of this promising new agent.

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