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Phase II Trial of Autologous Tumor Vaccination, Anti-CD3-Activated Vaccine-Primed Lymphocytes, and Interleukin-2 in Stage IV Renal Cell Cancer

Alfred E. Chang, Qiao Li, Guihua Jiang, Donna M. Sayre, Thomas M. Braun, Bruce G. Redman

From the Departments of Surgery, Biostatistics, and Internal Medicine, University of Michigan, Ann Arbor, MI.

Address reprint requests to Alfred Chang, MD, 3302 Cancer Center, 1500 E Medical Center Dr, Ann Arbor, MI 48109; email: aechang{at}umich.edu.

Purpose: Previous preclinical and clinical studies have demonstrated that autologous tumor vaccines can induce relatively specific tumor-reactive T cells in draining lymph nodes. The adoptive transfer of these cells can result in tumor regression.

Patients and Methods: Patients with stage IV renal cell cancer (RCC) were vaccinated with irradiated autologous tumor cells admixed with Calmette-Guérin bacillus. Approximately 7 days later, vaccine-primed lymph nodes (VPLNs) were harvested and the lymphoid cells secondarily activated with anti-CD3 monoclonal antibody and expanded in interleukin 2 (IL-2). The activated cells were subsequently infused intravenously along with the concomitant administration of bolus IL-2 (360,000 U/kg intravenously x 15 doses).

Results: Thirty-nine patients were entered onto the study, of whom 34 completed an initial course of cell therapy consisting of a mean (SEM) number of 4.3 (2.2) x 10¹⁰ VPLN cells. Among subjects who received cell therapy, there were nine responses (four complete responses [CRs] and five partial responses [PRs]), for an overall response rate of 27%. The durations of the CRs were > 48, 45, > 35, and 12 months, and the durations of the PRs were > 63, 48, 15, 12, and 4 months. Cultured tumor cells were available to assess in vitro cytokine release of VPLN cells in 24 subjects. The median cytokine release ratio of interferon gamma (IFN) to IL-10 for responders and nonresponders was 992 and 5, respectively, which was significantly different (P = .047).

Conclusion: The treatment protocol resulted in durable tumor responses in patients with advanced RCC. The ratio of IFN and IL-10 cytokines released in response to tumor by the VPLN cells was a significant correlate with tumor response.

Supported in part by National Institutes of Health grants CA69102 and MO1-RR00042 and by the Gillson Longenbaugh Foundation.

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