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Clinical Results and Characterization of Tumor-infiltrating Lymphocytes with or without Recombinant Interleukin 2 in Human Metastatic Renal Cell Carcinoma¹

Department of Experimental Therapeutics [R. M. B., J. S. S., V. G.], Department of Hematology and Medical Oncology [R. M. B., W. S., S. M., G. T. B.], Department of Pathology [R. M. B., R. T.], Department of General Medical Sciences [P. R., J. A., J. S., J. F.], Department of Biostatistics and Epidemiology [J. B., L. B.], and Department of Urology [E. P.], The Cleveland Clinic, Cleveland, Ohio 44195-5236

A Phase I trial of tumor-infiltrating lymphocytes (TIL) expanded in vitro and administered on Days 1 and 8, with or without continuous infusion recombinant interleukin 2 (rIL-2) in 25 patients with metastatic renal cell carcinoma, was conducted. Eighteen of the 25 eligible patients were treated with TIL and escalating doses of rIL-2 (0.0, 3.0, 4.5 x 10⁶ units/m²) on Days 1 to 5 and 8 to 12. Dose-limiting toxicity was pulmonary, and the maximum tolerated dose of rIL-2 was 3.0 x 10⁶ units/m². No clinical responses were observed. Immunological monitoring of peripheral blood lymphocytes demonstrated significant increases in CD3+ and CD56+ cells, including the activated T-cell subsets. Phenotypic analysis of cultured TILs demonstrated significant heterogeneity and the presence of CD3+CD4+ and CD3+CD8+ T-cells, with CD3-CD56+ and CD3+CD56+ populations also present. The majority of cultured TILs expressed HLA-DR and CD45RO, with a variable number expressing CD25. The rIL-2-expanded TILs possessed cytotoxicity against allogeneic and autologous tumor, with cytolytic activity against only autologous tumor seen in one patient. Results demonstrate that in vitro expansion of TILs is possible, but further studies are needed to define the biology of TILs in renal cancer and to isolate and expand tumor-specific T-cells.

¹ This investigation was supported in part by grants from The Cleveland Foundation and by Grant NO1-CM-47673-03.

² To whom requests for reprints should be addressed, at Department of Experimental Therapeutics, The Cleveland Clinic Cancer Center, One Clinic Center, 9500 Euclid Avenue, Cleveland, OH 44195-5236.

³ Present address: BRMP, Division of Cancer Treatment, National Cancer Institute, Frederick Cancer Research Facility, 501 W. Seventh Street, Frederick, MD 21701.

⁴ Present address: Harper Professional Bldg., 4160 John R., Suite 1017, Detroit, MI 48201.

Received 2/26/91. Accepted 6/10/91.

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