Phase I/II trial of an allogeneic cellular immunotherapy in hormone-naïve prostate cancer
| Autor: | William G. Nelson, Michael A. Carducci, Barbara A. Biedrzycki, Flavia Borellini, Kristen Hege, Jonathan W. Simons, Bahar Mikhak, Richard C. Mulligan, Michael Lim, Steven Piantadosi, Shirley M. Clift, Dale G. Ando |
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| Rok vydání: | 2006 |
| Předmět: |
Oncology
Male Cancer Research medicine.medical_specialty Injections Intradermal medicine.medical_treatment Cancer Vaccines Risk Assessment Antigen-Antibody Reactions Prostate cancer Antigen Prostate Antigens Neoplasm Recurrence Internal medicine Cell Line Tumor LNCaP medicine Humans Aged Neoplasm Staging PSA Velocity business.industry Granulocyte-Macrophage Colony-Stimulating Factor Immunotherapy Active Prostatic Neoplasms Immunotherapy Middle Aged Prostate-Specific Antigen medicine.disease GVAX medicine.anatomical_structure Treatment Outcome Cancer cell Immunology Neoplasm Recurrence Local business |
| Zdroj: | Clinical cancer research : an official journal of the American Association for Cancer Research. 12(11 Pt 1) |
| ISSN: | 1078-0432 |
| Popis: | 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 × 108 GM-CSF gene–transduced, irradiated, cancer cells (6 × 107 LNCaP cells and 6 × 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. |
| Databáze: | OpenAIRE |
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