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A Phase I Trial of CD3/CD28-activated T Cells (Xcellerated T Cells) and Interleukin-2 in Patients with Metastatic Renal Cell Carcinoma¹

University of Washington, Seattle, Washington 98109-1023 [J. A. T.]; University of California-Los Angeles Medical Center, Los Angeles, California [R. A. F.]; and Xcyte Therapies, Inc., Seattle, Washington [C. S-S., R. J. B., M. W. F.]

Purpose: Xcellerated T Cells (Xcyte Therapies, Seattle, WA) are autologous T cells that have been activated and expanded ex vivo using antibodies to CD3 and CD28 coimmobilized on magnetic beads. This study assessed the safety, immunostimulatory effects, and antitumor activity of Xcellerated T Cells and interleukin-2 (IL-2) in patients with metastatic renal cell carcinoma (RCC).

Experimental Design: Twenty-six patients with measurable metastatic RCC after prior nephrectomy underwent leukapheresis. Peripheral blood lymphocytes were stimulated ex vivo for 8 days. Two cycles of therapy separated by 28 days were planned, with each cycle consisting of i.v. Xcellerated T Cells on day 1 and s.c. IL-2 at 10 x 10⁶ units on days 1–10.

Results: Forty-nine cycles of therapy were administered to 25 patients. A mean (±SD) of 21.8 x 10⁹ (±5.4 x 10⁹) Xcellerated T Cells were administered each cycle. The infused cells were 94% ± 3% CD3⁺, 64 ± 12% CD4⁺, and 25 ± 12% CD8⁺ (mean ± SD). Adverse events (most commonly, fever and an influenza-like syndrome) were mild to moderate. Two patients developed significantly elevated human antimouse antibody titers (HAMA). No complete or partial clinical responses were observed. However, two patients experienced significant tumor regression in bone metastases. Median survival was 21 months. The number of cells infused correlated with the peak absolute lymphocyte count achieved, and there was a trend to increased postinfusion survival in patients achieving higher peak absolute lymphocyte counts.

Conclusions: Adoptive immunotherapy with Xcellerated T Cells and IL-2 can be carried out safely on an outpatient basis in patients with advanced RCC. Further investigation of this therapy is warranted.

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