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Antiproliferative and Antitumor Effects of -Interferon in Renal Cell Carcinomas: Correlation with the Expression of a Kidney-associated Differentiation Glycoprotein¹

Laboratory of Mammalian Cell Transformation [D. M. N., S. B., A. P. A.], Division of Solid Tumor Oncology, Department of Medicine [D. M. N.], and Laboratory of Human Cancer Immunology [N. H. B.], Memorial Sloan-Kettering Cancer Center, New York, New York 10021; The Rockefeller University, New York, New York [L. M. P.]; and Division of Urology, Department of Surgery, New York Hospital-Cornell University Medical Center, New York, New York [N. H. B.]

Human leukocyte -interferon (IFN-) has significant antitumor activity in advanced renal cell carcinoma (RC), with approximately 15% (range, 5 to 29%) of patients subjected to IFN- therapy exhibiting a major objective response. We assayed 16 RC cell lines for intrinsic sensitivity to the growth-inhibitory effects of recombinant IFN-. Similar to results observed in patients, cultured RCs could be divided into those that are inhibited by IFN- and those that are not. In addition, the IFN--sensitive or -resistant phenotype of cultured RCs was correlated with surface expression of six unrelated kidney-associated differentiation antigens. The expression of one antigen, a M_r 160,000 glycoprotein (gp160), was found to correlate with resistance to IFN-. Proliferation of seven RC cell lines expressing gp160 (gp160⁺) was not significantly inhibited by IFN- at concentrations as high as 3000 units/ml. In contrast, proliferation of eight of nine RC cell lines lacking expression of gp160 (gp160^-) was markedly inhibited by IFN-. The effect of IFN- gp160⁺ and gp160^– RC xenografts in nu/nu mice was examined. In separate experiments, two gp160⁺ RC cell lines and five gp160^– RC cell lines were injected s.c. into nu/nu mice; one half of the mice were subsequently treated with 10⁶ units of IFN- i.p. 3 times a wk, and one half received no IFN-. Tumors appeared at the sites of inoculation in all mice given injections of gp160⁺ RC cell lines within 10 to 25 days regardless of INF- therapy. Mice given injections of gp160^– RC cell lines, but not receiving IFN-, also formed tumors. In contrast, gp160^– RC cell lines injected into mice that were treated with IFN- exhibited a marked sensitivity, as demonstrated by either no tumor formation or delayed tumor formation. We conclude that the absence of gp160 expression by RCs may be predictive of sensitivity to the antitumor effects of IFN- and, thus, provide a basis for identifying IFN-responsive patients.

¹ This work was supported in part by the Charles H. Revson Foundation, the American Philosophical Society, a Young Investigator Award from the American Society of Clinical Oncology, The Society of Memorial Sloan-Kettering Cancer Center, and NIH Research Grant GM36716. D. M. N. is a Charles H. Revson Clinical Scholar in Biomedical Research, an American Philosophical Society Daland Fellow, and a 1988 Young Investigator of the American Society of Clinical Oncology. L. M. P. in a Scholar of the Leukemia Society of America. S. B. is a recipient of an American Urological Association Summer Student Fellowship.

² To whom requests for reprints should be addressed, at Memorial Sloan Kettering Cancer Center, Box 167, 1275 York Avenue, New York, NY 10021.

Received 12/21/89. Revised 3/ 9/90.

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