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Synergistic Antitumor Activity of Taxol and Immunotoxin SS1P in Tumor-Bearing Mice

Authors' Affiliations: ¹ Laboratory of Molecular Biology, Center for Cancer Research, National Cancer Institute, and ² Nuclear Medicine Department, Warren G. Magnuson Clinical Center, NIH, Bethesda, Maryland

Requests for reprints: Ira Pastan, Laboratory of Molecular Biology, Room 5106, 37 Convent Drive, Bethesda, MD 20892-4264. Phone: 301-496-4797; Fax: 301-402-1344; E-mail: pastani{at}mail.nih.gov.

Purpose: To investigate the combined antitumor activity in mice of immunotoxin SS1P and Taxol.

Methods: Immunodeficient mice were implanted with A431/K5 tumors expressing mesothelin. Established tumors were treated i.v. with immunotoxin SS1P alone, i.p. with Taxol alone, or with the two agents together. SS1P was radiolabeled with ¹¹¹In and used to study the effect of Taxol on its uptake by A431/K5 tumors.

Results: Using doses at which either agent alone caused stabilization of tumor growth, the combination was synergistic causing long-lasting complete remissions in many animals. In contrast, synergy was not observed when the same cells were treated with these agents in vitro. Tumor uptake of ¹¹¹In-SS1P was not affected by treatment with Taxol.

Conclusion: The combination of Taxol and SS1P exerts a synergistic antitumor effect in animals but not in cell culture. This effect is not secondary to increased tumor uptake of the immunotoxin. Synergy could be due to improved immunotoxin distribution within the tumor or could involve factors released by other cell types in the tumors.

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