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Phase I/II Trial of an Allogeneic Cellular Immunotherapy in Hormone-Naïve Prostate Cancer

Authors' Affiliations: ¹ Winship Cancer Institute, Emory University School of Medicine, Atlanta, Georgia; ² Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, Maryland; ³ Harvard Medical School, Boston, Massachusetts; and ⁴ Cell Genesys, Incorporated, South San Francisco, California

Requests for reprints: Jonathan W. Simons, Winship Cancer Institute, Emory University, Suite B4100, 1365 Clifton Road, Atlanta, GA 30322. Email: jonathan_simons{at}emory.org.

Purpose: To determine the toxicity, immunologic, and clinical activity of immunotherapy with irradiated, allogeneic, prostate cancer cells expressing granulocyte macrophage colony-stimulating factor (GM-CSF) in patients with recurrent prostate cancer.

Patients and Methods: A single-institution phase I/II trial was done in hormone therapy–naïve patients with prostate-specific antigen (PSA) relapse following radical prostatectomy and absence of radiologic metastases. Treatments were administered weekly via intradermal injections of 1.2 x 10⁸ GM-CSF gene–transduced, irradiated, cancer cells (6 x 10⁷ LNCaP cells and 6 x 10⁷ PC-3 cells) for 8 weeks.

Results: Twenty-one patients were enrolled and treated. Toxicities included local injection-site reactions, pruritus, and flu-like symptoms. One patient had a partial PSA response of 7-month duration. At 20 weeks post first treatment, 16 of 21 (76%) patients showed a statistically significant decrease in PSA velocity (slope) compared with prevaccination (P < 0.001). Injection site biopsies showed intradermal infiltrates consisting of CD1a⁺ dendritic cells and CD68⁺ macrophages, similar to previous clinical trials using autologous GM-CSF-transduced cancer cells. Posttreatment, patients developed new oligoclonal antibodies reactive against at least five identified antigens present in LNCaP or PC-3 cells. A high-titer antibody response against a 250-kDa antigen expressed on normal prostate epithelial cells was induced in a patient with partial PSA remission; titers of this antibody decreased when treatment ended, and subsequent PSA relapse occurred.

Conclusions: This non-patient-specific prostate cancer immunotherapy has a favorable safety profile and is immunologically active. Continued clinical investigation at higher doses and with longer boosting schedules is warranted.

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