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

• Published in: Clinical cancer research Vol. 12; no. 11; pp. 3394 - 3401
• Main Authors: SIMONS, Jonathan W, CARDUCCI, Michael A, MULLIGAN, Richard, NELSON, William G, MIKHAK, Bahar, LIM, Michael, BIEDRZYCKI, Barbara, BORELLINI, Flavia, CLIFT, Shirley M, HEGE, Kristen M, ANDO, Dale G, PIANTADOSI, Steven
• Format: Journal Article
• Language: English
• Published: Philadelphia, PA American Association for Cancer Research 01.06.2006
• Subjects: Aged; Antigen-Antibody Reactions; Antigens, Neoplasm - genetics; Antigens, Neoplasm - immunology; Antineoplastic agents; Biological and medical sciences; Cancer Vaccines - therapeutic use; Cell Line, Tumor; cellular immunotherapy; Granulocyte-Macrophage Colony-Stimulating Factor - biosynthesis; Granulocyte-Macrophage Colony-Stimulating Factor - genetics; GVAX; Gynecology. Andrology. Obstetrics; Humans; Immunotherapy, Active - methods; Injections, Intradermal; Male; Male genital diseases; Medical sciences; Middle Aged; Neoplasm Recurrence, Local - immunology; Neoplasm Recurrence, Local - surgery; Neoplasm Recurrence, Local - therapy; Neoplasm Staging; Nephrology. Urinary tract diseases; Pharmacology. Drug treatments; prostate cancer; Prostate-Specific Antigen - blood; Prostatic Neoplasms - immunology; Prostatic Neoplasms - surgery; Prostatic Neoplasms - therapy; Recurrence; Risk Assessment; Treatment Outcome; Tumors; Tumors of the urinary system; Urinary tract. Prostate gland; Human; Hormone; Urinary system disease; Prostate disease; Malignant tumor; In vitro; Allogeneic system; Treatment; Immunotherapy; Phase II trial; Phase I trial; Male genital diseases; Prostate cancer
• ISSN: 1078-0432; 1557-3265
• DOI: 10.1158/1078-0432.CCR-06-0145

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 × 10 8 GM-CSF gene–transduced, irradiated, cancer cells (6 × 10 7 LNCaP cells and 6 × 10 7 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.