Autologous dendritic cells transfected with prostate-specific antigen RNA stimulate CTL responses against metastatic prostate tumors

Axel Heiser, Doris Coleman, Jens Dannull, Donna Yancey, Margaret A. Maurice, Costas D. Lallas, Philipp Dahm, Donna Niedzwiecki, Eli Gilboa, Johannes Vieweg

Research output: Contribution to journalArticle

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Abstract

Autologous dendritic cells (DCs) transfected with mRNA encoding prostate-specific antigen (PSA) are able to stimulate potent, T cell-mediated antitumor immune responses in vitro. A phase I trial was performed to evaluate this strategy for safety, feasibility, and efficacy to induce T cell responses against the self-protein PSA in patients with metastatic prostate cancer. In 13 study subjects, escalating doses of PSA mRNA-transfected DCs were administered with no evidence of dose-limiting toxicity or adverse effects, including autoimmunity. Induction of PSA-specific T cell responses was consistently detected in all patients, suggesting in vivo bioactivity of the vaccine. Vaccination was further associated with a significant decrease in the log slope PSA in six of seven subjects; three patients that could be analyzed exhibited a transient molecular clearance of circulating tumor cells. The demonstration of vaccine safety, successful in vivo induction of PSA-specific immunity, and impact on surrogate clinical endpoints provides a scientific rationale for further clinical investigation of RNA-transfected DCs in the treatment of human cancer.

Original languageEnglish
Pages (from-to)409-417
Number of pages9
JournalJournal of Clinical Investigation
Volume109
Issue number3
DOIs
StatePublished - Feb 23 2002
Externally publishedYes

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Prostate-Specific Antigen
Dendritic Cells
Prostate
RNA
Neoplasms
T-Lymphocytes
Vaccines
Circulating Neoplastic Cells
Safety
Messenger RNA
Autoimmunity
Immunity
Prostatic Neoplasms
Vaccination
Biomarkers
Proteins

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Autologous dendritic cells transfected with prostate-specific antigen RNA stimulate CTL responses against metastatic prostate tumors. / Heiser, Axel; Coleman, Doris; Dannull, Jens; Yancey, Donna; Maurice, Margaret A.; Lallas, Costas D.; Dahm, Philipp; Niedzwiecki, Donna; Gilboa, Eli; Vieweg, Johannes.

In: Journal of Clinical Investigation, Vol. 109, No. 3, 23.02.2002, p. 409-417.

Research output: Contribution to journalArticle

Heiser, A, Coleman, D, Dannull, J, Yancey, D, Maurice, MA, Lallas, CD, Dahm, P, Niedzwiecki, D, Gilboa, E & Vieweg, J 2002, 'Autologous dendritic cells transfected with prostate-specific antigen RNA stimulate CTL responses against metastatic prostate tumors', Journal of Clinical Investigation, vol. 109, no. 3, pp. 409-417. https://doi.org/10.1172/JCI200214364
Heiser, Axel ; Coleman, Doris ; Dannull, Jens ; Yancey, Donna ; Maurice, Margaret A. ; Lallas, Costas D. ; Dahm, Philipp ; Niedzwiecki, Donna ; Gilboa, Eli ; Vieweg, Johannes. / Autologous dendritic cells transfected with prostate-specific antigen RNA stimulate CTL responses against metastatic prostate tumors. In: Journal of Clinical Investigation. 2002 ; Vol. 109, No. 3. pp. 409-417.
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abstract = "Autologous dendritic cells (DCs) transfected with mRNA encoding prostate-specific antigen (PSA) are able to stimulate potent, T cell-mediated antitumor immune responses in vitro. A phase I trial was performed to evaluate this strategy for safety, feasibility, and efficacy to induce T cell responses against the self-protein PSA in patients with metastatic prostate cancer. In 13 study subjects, escalating doses of PSA mRNA-transfected DCs were administered with no evidence of dose-limiting toxicity or adverse effects, including autoimmunity. Induction of PSA-specific T cell responses was consistently detected in all patients, suggesting in vivo bioactivity of the vaccine. Vaccination was further associated with a significant decrease in the log slope PSA in six of seven subjects; three patients that could be analyzed exhibited a transient molecular clearance of circulating tumor cells. The demonstration of vaccine safety, successful in vivo induction of PSA-specific immunity, and impact on surrogate clinical endpoints provides a scientific rationale for further clinical investigation of RNA-transfected DCs in the treatment of human cancer.",
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AU - Coleman, Doris

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AU - Yancey, Donna

AU - Maurice, Margaret A.

AU - Lallas, Costas D.

AU - Dahm, Philipp

AU - Niedzwiecki, Donna

AU - Gilboa, Eli

AU - Vieweg, Johannes

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