Go to JCI Insight
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Publication alerts by email
  • Advertising
  • Job board
  • Contact
  • Clinical Research and Public Health
  • Current issue
  • Past issues
  • By specialty
    • COVID-19
    • Cardiology
    • Gastroenterology
    • Immunology
    • Metabolism
    • Nephrology
    • Neuroscience
    • Oncology
    • Pulmonology
    • Vascular biology
    • All ...
  • Videos
    • Conversations with Giants in Medicine
    • Video Abstracts
  • Reviews
    • View all reviews ...
    • Pancreatic Cancer (Jul 2025)
    • Complement Biology and Therapeutics (May 2025)
    • Evolving insights into MASLD and MASH pathogenesis and treatment (Apr 2025)
    • Microbiome in Health and Disease (Feb 2025)
    • Substance Use Disorders (Oct 2024)
    • Clonal Hematopoiesis (Oct 2024)
    • Sex Differences in Medicine (Sep 2024)
    • View all review series ...
  • Viewpoint
  • Collections
    • In-Press Preview
    • Clinical Research and Public Health
    • Research Letters
    • Letters to the Editor
    • Editorials
    • Commentaries
    • Editor's notes
    • Reviews
    • Viewpoints
    • 100th anniversary
    • Top read articles

  • Current issue
  • Past issues
  • Specialties
  • Reviews
  • Review series
  • Conversations with Giants in Medicine
  • Video Abstracts
  • In-Press Preview
  • Clinical Research and Public Health
  • Research Letters
  • Letters to the Editor
  • Editorials
  • Commentaries
  • Editor's notes
  • Reviews
  • Viewpoints
  • 100th anniversary
  • Top read articles
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Publication alerts by email
  • Advertising
  • Job board
  • Contact
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.
View: Text | PDF
Article

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

  • Text
  • PDF
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

×

Figure 1

Options: View larger image (or click on image) Download as PowerPoint
Incubation of immature DCs with PSA RNA provides a maturation stimulus. ...
Incubation of immature DCs with PSA RNA provides a maturation stimulus. (a) Upregulation of CD83 expression by immature DCs in the presence of increasing PSA mRNA concentrations. (b–e) Immature DCs were incubated for 45 minutes in the presence of 20 μg/ml of PSA mRNA and analyzed after 48 hours by flow cytometry for expression of the DC-specific marker CD1a and the DC maturation marker CD83, respectively. (b) Staining with isotype immunoglobulins IgG2b-FITC and IgG1-PE (isotype control). (c) DCs incubated in the absence of PSA mRNA (untreated). (d) DCs incubated with PSA mRNA that had been treated for 1 hour at 37°C with 10 μg/ml RNase A (PSA-RNA + RNase A), and (e) DCs incubated in the presence of PSA mRNA. One representative experiment out of three independent experiments is presented.

Copyright © 2025 American Society for Clinical Investigation
ISSN: 0021-9738 (print), 1558-8238 (online)

Sign up for email alerts