Immunotherapy with Autologous, Human Dendritic Cells Transfected with Carcinoembryonic Antigen mRNA: ORIGINAL ARTICLE
Abstract
Immunizations with dendritic cells (DC) transfected with RNA encoding tumor antigens induce potent tumor antigen-specific immune responses in vitro and in murine models. We performed a phase I study of patients with advanced carcinoembryonic antigen (CEA)-expressing malignancies followed by a phase II study of patients with resected hepatic metastases of colon cancer to assess safety and feasibility of administering autologous DC loaded with CEA mRNA. The immunizations were well tolerated. Of the 24 evaluable patients in the dose-escalation phase, there was 1 complete response (by tumor marker), 2 minor responses, 3 with stable disease, and 18 with progressive disease. In the phase II study, 9 of 13 patients have relapsed at a median of 122 days. Evidence of an immunologic response was demonstrated in biopsies of DC injection sites and peripheral blood of selected patients. We conclude that it is feasible and safe to administer mRNA-loaded DC to patients with advanced malignancies.
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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 [11]
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- Authors
- Morse, M. A., Nair, S. K., Mosca, P. J., Hobeika, A. C., Clay, T. M., Deng, Y., Boczkowski, D., Proia, A., Neidzwiecki, D., Clavien#, P.-A., Hurwitz, H. I., Schlom, J., Gilboa, E., & Lyerly, H. K.
- Affiliations
- Duke Medical Center (US)
- Eastern Virginia Medical School (US)
- National Institutes of Health (US)
- ORCID
- Venue
- Cancer Investigation
- Publisher
- Informa UK Limited
- Published
- 2003-01
- Volume
- 21
- Issue
- 3
- Pages
- 341-349
- ISSN
- 0735-7907 (ISSN-L)
- 1532-4192
- OpenAlex
- W2117503715
- Cited by
- 177
- References
- 0
- Citations by year
- 2026: 4 · 2025: 8 · 2024: 5 · 2023: 6 · 2022: 4 · 2021: 7 · 2020: 7 · 2019: 2 · 2018: 5 · 2017: 2 · 2016: 4 · 2015: 5 · 2014: 11 · 2013: 11 · 2012: 8
- FWCI
- 3.85
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Cancer Investigation (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (1r01ca075472-01a1)
- National Cancer Institute (P01CA078673, R01-CA75472-01, P01-CA78673-01)
- National Center for Research Resources (M01RR000030)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biotechnology › Cancer Research and Treatments
- Health Sciences › Medicine › Oncology › Cancer Immunotherapy and Biomarkers
- Keywords
- dendritic cell immunotherapy, carcinoembryonic antigen, mRNA transfection, autologous dendritic cells, colon cancer, liver metastasis, dose escalation, advanced cancer
- MeSH terms
- Adult, Aged, Carcinoembryonic Antigen, Colonic Neoplasms, Dendritic Cells, Dose-Response Relationship, Drug, Female, Humans, Immunotherapy, Leukapheresis, Liver Neoplasms, Male, Middle Aged, Recombinant Proteins, RNA, Messenger, Transfection, Transplantation, Autologous, Survival Analysis
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