Autologous dendritic cells transfected with prostate-specific antigen RNA stimulate CTL responses against metastatic prostate tumors
Open accessAbstract
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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The gene of interest is used with its autochthonous noncoding regions or is flanked by the untranslated region of the human or Xenopus laevis beta-globin gene.
“The gene of interest is used with its autochthonous noncoding regions 12 or is flanked by the untranslated region (UTR) of the human or Xenopus laevis -globin gene.14”
From Modification of antigen-encoding RNA increases stability, translational efficacy, and T-cell stimulatory capacity of dendritic cells (2006) · cites this paper as [12]
Antigen-encoding RNA constructs used currently for preclinical studies have poly(A) tails measuring 30 to 70 nucleotides, whereas those administered in clinical trials measure 64 nucleotides.
“Antigen-encoding RNA constructs used currently for preclinical studies have poly(A) tails measuring 30 to 70 nucleotides in length, 4,5 whereas those administered in clinical trials measure 64 nucleotides in length.8,12”
From Modification of antigen-encoding RNA increases stability, translational efficacy, and T-cell stimulatory capacity of dendritic cells (2006) · cites this paper as [12]
Early clinical trials of RNA-based vaccines showed feasibility, lack of toxicity, and promising efficacy based on immunologic and clinical read-outs.
“Early clinical trials showed feasibility, lack of toxicity, and promising efficacy based on immunologic and clinical read-outs.[8][9][10][11][12]”
From Modification of antigen-encoding RNA increases stability, translational efficacy, and T-cell stimulatory capacity of dendritic cells (2006) · cites this paper as [12]
Vectors used currently for preclinical and clinical studies resort either to UTRs of β-globin or to autochthonous UTRs of the antigen they deliver, which are not further characterized in terms of their impact on RNA stability.
“Vectors used currently for preclinical and clinical studies resort either to UTRs of -globin 5,14,23 or to autochthonous UTRs of the antigen they want to deliver, 12 which are not further characterized in terms of their impact on RNA stability.”
From Modification of antigen-encoding RNA increases stability, translational efficacy, and T-cell stimulatory capacity of dendritic cells (2006) · cites this paper as [12]
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- Authors
- Heiser, A., Coleman, D., Dannull, J., Yancey, D., Maurice, M. A., Lallas, C. D., Dahm, P., Niedzwiecki, D., Gilboa, E., & Vieweg, J.
- Affiliations
- Duke University (US)
- Corresponding author
- Vieweg, Johannes
- Venue
- Journal of Clinical Investigation
- Published
- 2002-02-01
- Volume
- 109
- Issue
- 3
- Pages
- 409-417
- ISSN
- 0021-9738 (ISSN-L)
- PMC
- PMC150859
- OpenAlex
- W2054248438
- Cited by
- 562
- References
- 0
- Citations by year
- 2026: 12 · 2025: 13 · 2024: 20 · 2023: 18 · 2022: 18 · 2021: 11 · 2020: 21 · 2019: 7 · 2018: 11 · 2017: 7 · 2016: 9 · 2015: 10 · 2014: 9 · 2013: 15 · 2012: 18
- FWCI
- 18.92
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Journal of Clinical Investigation (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- NSUWorks (Nova Southeastern University) (submittedVersion)
- Funders
- National Institutes of Health (MO1-RR-30)
- National Cancer Institute (KO8-CA-9322)
- National Center for Research Resources (M01RR000030, MO 1 RR-30)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Prostate Cancer Treatment and Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biotechnology › Cancer Research and Treatments
- Keywords
- dendritic cell vaccine, prostate-specific antigen, mRNA transfection, autologous dendritic cells, metastatic prostate cancer, CTL response, cancer immunotherapy, vaccine safety, circulating tumor cells
- MeSH terms
- Dendritic Cells, Humans, Male, Prostatic Neoplasms, RNA, Messenger, Safety, T-Lymphocytes, Cytotoxic, Transfection, Transplantation, Autologous, Immunotherapy, Active, Prostate-Specific Antigen, Cancer Vaccines
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