Autologous dendritic cells transfected with prostate-specific antigen RNA stimulate CTL responses against metastatic prostate tumors
Axel Heiser, … , Eli Gilboa, Johannes Vieweg
Axel Heiser, … , Eli Gilboa, Johannes Vieweg
Published February 1, 2002
Citation Information: J Clin Invest. 2002;109(3):409-417. https://doi.org/10.1172/JCI14364.
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Article

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

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.

Authors

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

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In vivo induction of PSA-specific T cell responses. PBMCs obtained at ba...
In vivo induction of PSA-specific T cell responses. PBMCs obtained at baseline (PSA, KK pre) and after three vaccination cycles (PSA, KK post) using PSA RNA–transfected DCs were cultured overnight with PSA or kallikrein protein (5 μg/ml). The specific T cell frequencies in each of the evaluable patients treated at a low dose level (107 cells; patient 2, 3, and 5), medium dose level (3 × 107 cells; patient 6, 7, and 9), or high dose level (5 × 107 cells; patient 11 and 13) is expressed as the number of spot-forming cells per 5 × 105 PBMCs seeded in each well.