TY - JOUR
T1 - Phase I/II trial of an allogeneic cellular immunotherapy in hormone-naïve prostate cancer
AU - Simons, Jonathan W.
AU - Carducci, Michael A.
AU - Mikhak, Bahar
AU - Lim, Michael
AU - Biedrzycki, Barbara
AU - Borellini, Flavia
AU - Clift, Shirley M.
AU - Hege, Kristen M.
AU - Ando, Dale G.
AU - Piantadosi, Steven
AU - Mulligan, Richard
AU - Nelson, William G.
PY - 2006/6/1
Y1 - 2006/6/1
N2 - 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. Post-treatment, 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.
AB - 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. Post-treatment, 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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U2 - 10.1158/1078-0432.CCR-06-0145
DO - 10.1158/1078-0432.CCR-06-0145
M3 - Article
C2 - 16740763
AN - SCOPUS:33745219416
VL - 12
SP - 3394
EP - 3401
JO - Clinical Cancer Research
JF - Clinical Cancer Research
SN - 1078-0432
IS - 11 I
ER -