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Immunological Effects of Treatment with Sequential Administration of Recombinant Interferon and in Patients with Metastatic Renal Cell Carcinoma during a Phase I Trial¹

Division of Medical Oncology, Department of Medicine [M. S. E., S. N., J. M. K.], Division of Urology, Department of Surgery [M. S. E., R. R. B.], and Departments of Radiology [L. M. M.], Pathology [B. B., T. W.], Biostatistics [W. G., R. D.], and Epidemiology, Graduate School of Public Health [L. T-E.], University of Pittsburgh, School of Medicine and the Pittsburgh Cancer Institute, Pittsburgh, Pennsylvania 15213

Many anticancer mechanisms of the interferons have been proposed but none have been associated with clinical response to date. The biological activities of the interferons in vivo have included effects upon the natural killer cell, T- and B-lymphocytes, and macrophages. This report details a prospective study of the immunological effects on peripheral blood mononuclear cells of sequentially administered recombinant (r) interferon (IFN) and rIFN in 28 patients with metastatic renal cell carcinoma. Natural killer cell activity, T-cell phenotype (CD4, CD8, CD56, CD16, CD4/HLA-DR, CD8/HLA-DR, CD56/HLA-DR) and 2',5'-oligoadenylate synthetase were measured prior to therapy, during therapy, and following completion of treatment. Statistical analysis of all parameters was performed for the entire group, by individual patient, by dosage, by time, and by clinical response. An overall significant depression in natural killer cell activity and in the percentage of circulating CD56, CD16, and CD8+ cells were noted. Significant increases in 2',5'-oligoadenylate synthetase and in the percentage of circulating CD4 cells were also noted. Although an association between the magnitude of change in percentage of CD16+ cells and 2',5'-oligoadenylate synthetase and dosage of rIFN and rIFN , respectively, was observed, optimal biological dose of this sequence of rIFNs could not be determined due to the limited number of patients. A decrease in the percentage of circulating CD8+ cells was observed among patients with objective clinical response (partial and complete). Sequentially administered rIFN and rIFN can modulate immunological parameters in vivo in patients with metastatic renal cell carcinoma. A fall in percentage of circulating CD8+ cell is associated with response and suggests that this sequence of rIFN and rIFN might influence T-cell mediated antitumor activity.

¹ Supported by National Cancer Institute Grant NO-1-CM-47681-01.

² To whom requests for reprints should be addressed, at Division of Hematology/Oncology, Norris Cotton Cancer Center, Dartmouth-Hitchcock Medical Center, One Medical Center Drive, Lebanon, NH 03756.

Received 5/17/91. Accepted 12/ 2/91.

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