Phase I/II trial of an allogeneic cellular immunotherapy in hormone-naïve prostate cancer

Jonathan W. Simons, Michael A Carducci, Bahar Mikhak, Michael Lim, Barbara Biedrzycki, Flavia Borellini, Shirley M. Clift, Kristen M. Hege, Dale G. Ando, Steven Piantadosi, Richard Mulligan, William G Nelson

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
Pages (from-to)3394-3401
Number of pages8
JournalClinical Cancer Research
Volume12
Issue number11 I
DOIs
StatePublished - Jun 1 2006

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Immunotherapy
Prostatic Neoplasms
Hormones
Prostate-Specific Antigen
Granulocyte-Macrophage Colony-Stimulating Factor
Therapeutics
Antigens
Recurrence
Intradermal Injections
Injections
Antibodies
Pruritus
Prostatectomy
Dendritic Cells
Antibody Formation
Prostate
Neoplasms
Appointments and Schedules
Epithelial Cells
Macrophages

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Phase I/II trial of an allogeneic cellular immunotherapy in hormone-naïve prostate cancer. / Simons, Jonathan W.; Carducci, Michael A; Mikhak, Bahar; Lim, Michael; Biedrzycki, Barbara; Borellini, Flavia; Clift, Shirley M.; Hege, Kristen M.; Ando, Dale G.; Piantadosi, Steven; Mulligan, Richard; Nelson, William G.

In: Clinical Cancer Research, Vol. 12, No. 11 I, 01.06.2006, p. 3394-3401.

Research output: Contribution to journalArticle

Simons, JW, Carducci, MA, Mikhak, B, Lim, M, Biedrzycki, B, Borellini, F, Clift, SM, Hege, KM, Ando, DG, Piantadosi, S, Mulligan, R & Nelson, WG 2006, 'Phase I/II trial of an allogeneic cellular immunotherapy in hormone-naïve prostate cancer', Clinical Cancer Research, vol. 12, no. 11 I, pp. 3394-3401. https://doi.org/10.1158/1078-0432.CCR-06-0145
Simons, Jonathan W. ; Carducci, Michael A ; Mikhak, Bahar ; Lim, Michael ; Biedrzycki, Barbara ; Borellini, Flavia ; Clift, Shirley M. ; Hege, Kristen M. ; Ando, Dale G. ; Piantadosi, Steven ; Mulligan, Richard ; Nelson, William G. / Phase I/II trial of an allogeneic cellular immunotherapy in hormone-naïve prostate cancer. In: Clinical Cancer Research. 2006 ; Vol. 12, No. 11 I. pp. 3394-3401.
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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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