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Suppression of Tumor Growth in Vivo by Local and Systemic 90K Level Increase¹

Sugen, Inc., Redwood City, California 94063 [B. J., J. P., J. Z., L. G., J. J.]; Department of Molecular Biology, Max-Planck-Institut für Biochemie, Am Klopferspitz 18A, 82152 Martinsried, Germany [B. J., C. B., A. U.]; and Cattedra di Oncologia Medica, Universita G. D'Annunzio, Via dei Vestini, 6, 66100 Chieti, Italy [S. I.]

Expression levels of the immunostimulatory 90K antigen in mammary carcinoma, glioblastoma, and other tumor-derived cell lines inversely correlate with their tumorigenicity in athymic mice. Engineered enhancement of 90K expression results in significant (>80%) tumor growth inhibition, not by direct action on the tumor cell, but by stimulation of the residual cell-mediated immune defense of the nude mouse. Enhanced 90K level effects are both localized and systemic and involve induction of ICAM-1 and VCAM-1 in the tumor endothelium. The findings presented suggest a role for 90K as a molecular alarm signal for the body's cellular defense against pathogens, which in a subset of tumors is suppressed to allow cancer progression.

¹ This work was supported in part by grants (to S.I.) from Associazione Italiana per la Ricerca sul Cancro and Consiglio Nazionale Richerche Special Project "Applicazioni Cliniche della Ricerca Oncologica."

² To whom requests for reprints should be addressed.

Received 5/19/95. Accepted 6/14/95.

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