Priming tissue-specific cellular immunity in a phase I trial of autologous dendritic cells for prostate cancer

Patrick A. Burch, Jami K. Breen, Jan Craig Buckner, Dennis A. Gastineau, Judith S Kaur, Reiner L. Laus, Douglas J. Padley, Madhusudan V. Peshwa, Henry Clement Pitot, Ronald L. Richardson, Bouwien J. Smits, Pitsata Sopapan, George Strang, Frank H. Valone, Stanimir Vuk-Pavlović

Research output: Contribution to journalArticle

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Abstract

We attempted to induce therapeutic immunity against prostate-derived tissues in patients suffering from progressive hormone-refractory metastatic prostate carcinoma. Thirteen patients were treated with two infusions, 1 month apart, of autologous dendritic cells (APC8015) preexposed ex vivo to PA2024, a fusion protein consisting of human granulocyte/macrophage-colony stimulating factor (GM-CSF) and human prostatic acid phosphatase (PAP). The infusions were followed by three s.c. monthly doses of PA2024 without cells. Three groups of patients each received PA2024 at 0.3, 0.6, or 1.0 mg/injection. All Ps were two-sided. Treatment was well tolerated. After infusions of APC8015, patients experienced only mild (grade 1-2) short-lived fever and/or chills, myalgia, pain, and fatigue. One patient developed grade 3 fatigue. Four patients developed mild local reactions to s.c. PA2024. Twelve patients were evaluable for response to treatment. Circulating prostate-specific antigen levels dropped in three patients. T cells, drawn from patients after infusions of APC8015, but not before, could be stimulated in vitro by GM-CSF (P = 0.0004) and PAP (P = 0.0001), demonstrating broken immune tolerance against these two normal proteins. Injections of PA2024 did not influence the reactivity of T cells against PAP and GM-CSF. However, antibodies to GM-CSF and, to a much lesser extent, to PAP reached maximum titers only after two or even three injections of PA2024, showing that directly injected PA2024 was involved in stimulation of humoral immunity. Dendritic cells exposed to antigen ex vivo can induce antigen-specific cellular immunity in prostate cancer patients, warranting further studies of this mode of immunotherapy.

Original languageEnglish (US)
Pages (from-to)2175-2182
Number of pages8
JournalClinical Cancer Research
Volume6
Issue number6
StatePublished - Jun 2000

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Cellular Immunity
Dendritic Cells
Prostatic Neoplasms
Granulocyte-Macrophage Colony-Stimulating Factor
Injections
Fatigue
Prostate
T-Lymphocytes
Antigens
Chills
Immune Tolerance
Myalgia
Prostate-Specific Antigen
Humoral Immunity
Immunotherapy
Immunity
Proteins
Fever
Therapeutics
Hormones

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Burch, P. A., Breen, J. K., Buckner, J. C., Gastineau, D. A., Kaur, J. S., Laus, R. L., ... Vuk-Pavlović, S. (2000). Priming tissue-specific cellular immunity in a phase I trial of autologous dendritic cells for prostate cancer. Clinical Cancer Research, 6(6), 2175-2182.

Priming tissue-specific cellular immunity in a phase I trial of autologous dendritic cells for prostate cancer. / Burch, Patrick A.; Breen, Jami K.; Buckner, Jan Craig; Gastineau, Dennis A.; Kaur, Judith S; Laus, Reiner L.; Padley, Douglas J.; Peshwa, Madhusudan V.; Pitot, Henry Clement; Richardson, Ronald L.; Smits, Bouwien J.; Sopapan, Pitsata; Strang, George; Valone, Frank H.; Vuk-Pavlović, Stanimir.

In: Clinical Cancer Research, Vol. 6, No. 6, 06.2000, p. 2175-2182.

Research output: Contribution to journalArticle

Burch, PA, Breen, JK, Buckner, JC, Gastineau, DA, Kaur, JS, Laus, RL, Padley, DJ, Peshwa, MV, Pitot, HC, Richardson, RL, Smits, BJ, Sopapan, P, Strang, G, Valone, FH & Vuk-Pavlović, S 2000, 'Priming tissue-specific cellular immunity in a phase I trial of autologous dendritic cells for prostate cancer', Clinical Cancer Research, vol. 6, no. 6, pp. 2175-2182.
Burch, Patrick A. ; Breen, Jami K. ; Buckner, Jan Craig ; Gastineau, Dennis A. ; Kaur, Judith S ; Laus, Reiner L. ; Padley, Douglas J. ; Peshwa, Madhusudan V. ; Pitot, Henry Clement ; Richardson, Ronald L. ; Smits, Bouwien J. ; Sopapan, Pitsata ; Strang, George ; Valone, Frank H. ; Vuk-Pavlović, Stanimir. / Priming tissue-specific cellular immunity in a phase I trial of autologous dendritic cells for prostate cancer. In: Clinical Cancer Research. 2000 ; Vol. 6, No. 6. pp. 2175-2182.
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abstract = "We attempted to induce therapeutic immunity against prostate-derived tissues in patients suffering from progressive hormone-refractory metastatic prostate carcinoma. Thirteen patients were treated with two infusions, 1 month apart, of autologous dendritic cells (APC8015) preexposed ex vivo to PA2024, a fusion protein consisting of human granulocyte/macrophage-colony stimulating factor (GM-CSF) and human prostatic acid phosphatase (PAP). The infusions were followed by three s.c. monthly doses of PA2024 without cells. Three groups of patients each received PA2024 at 0.3, 0.6, or 1.0 mg/injection. All Ps were two-sided. Treatment was well tolerated. After infusions of APC8015, patients experienced only mild (grade 1-2) short-lived fever and/or chills, myalgia, pain, and fatigue. One patient developed grade 3 fatigue. Four patients developed mild local reactions to s.c. PA2024. Twelve patients were evaluable for response to treatment. Circulating prostate-specific antigen levels dropped in three patients. T cells, drawn from patients after infusions of APC8015, but not before, could be stimulated in vitro by GM-CSF (P = 0.0004) and PAP (P = 0.0001), demonstrating broken immune tolerance against these two normal proteins. Injections of PA2024 did not influence the reactivity of T cells against PAP and GM-CSF. However, antibodies to GM-CSF and, to a much lesser extent, to PAP reached maximum titers only after two or even three injections of PA2024, showing that directly injected PA2024 was involved in stimulation of humoral immunity. Dendritic cells exposed to antigen ex vivo can induce antigen-specific cellular immunity in prostate cancer patients, warranting further studies of this mode of immunotherapy.",
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