Results of a phase 1 study utilizing monocyte-derived dendritic cells pulsed with tumor RNA in children and young adults with brain cancer
Open accessAbstract
We conducted a phase 1 study of 9 pediatric patients with recurrent brain tumors using monocyte-derived dendritic cells pulsed with tumor RNA to produce antitumor vaccine (DCRNA) preparations. The objectives of this study included (1) establishing safety and feasibility and (2) measuring changes in general, antigen-specific, and tumor-specific immune responses after DCRNA. Dendritic cells were derived from freshly isolated monocytes after 7 days of culture with IL-4 and granulocyte-macrophage colony-stimulating factor, pulsed with autologous tumor RNA, and then cryopreserved. Patients received at least 3 vaccines, each consisting of an intravenous and an intradermal administration at biweekly intervals. The study showed that this method for producing and administering DCRNA from a single leukapheresis product was both feasible and safe in this pediatric brain tumor population. Immune function at the time of enrollment into the study was impaired in all patients tested. While humoral responses to recall antigens (diphtheria and tetanus) were intact in all patients, cellular responses to mitogen and recall antigens were below normal. Following DCRNA vaccine, 2 of 7 patients showed stable clinical disease and 1 of 7 showed a partial response. Two of 7 patients who were tested showed a tumor-specific immune response to DCRNA. This study showed that DCRNA vaccines are both safe and feasible in children with tumors of the central nervous system with a single leukapheresis.
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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 [9]
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- Sampson, J.H., Crotty, L.E., Lee, S., Archer, G.E., Ashley, D.M., Wikstrand, C.J., Hale, L.P., Small, C., Dranoff, G., Friedman, A.H., Friedman, H.S., and Bigner, D.D. (2000) Unarmed, tumor-specific monoclonal antibody effectively treats brain tumors. Proc. Natl. Acad. Sci. USA 97, 7503 - 7508.
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Holtkamp, S., Kreiter, S., Selmi, A., Simon, P., Koslowski, M., Huber, C., Türeci, O., & Sahin, U. (2006) · Blood · doi:10.1182/blood-2006-04-015024 · Cited by 625 · see citing works
An RNA toolbox for cancer immunotherapy
Pastor, F., Berraondo, P., Etxeberria, I., Frederick, J., Sahin, U., Gilboa, E., & Melero, I. (2018) · Nature Reviews Drug Discovery · doi:10.1038/nrd.2018.132 · Cited by 229 · see citing works
Himoudi, N., Wallace, R., Parsley, K. L., Gilmour, K., Barrie, A.-U., Howe, K., Dong, R., Sebire, N. J., Michalski, A., Thrasher, A. J., et al. (2012) · Clinical and Translational Oncology · doi:10.1007/s12094-012-0795-1 · Cited by 74 · see citing works
- Authors
- Caruso, D. A., Orme, L. M., Neale, A. M., Radcliff, F. J., Amor, G. M., Maixner, W., Downie, P., Hassall, T. E., Tang, M. L. K., & Ashley, D. M.
- Affiliations
- Royal Children's Hospital (AU)
- Children's Health Queensland Hospital and Health Service (AU)
- Corresponding author
- Caruso, Denise A.
- Venue
- Neuro-Oncology
- Publisher
- Oxford University Press (OUP)
- Published
- 2004-07-01
- Volume
- 6
- Issue
- 3
- Pages
- 236-246
- ISSN
- 1522-8517 (ISSN-L)
- 1523-5866
- PMC
- PMC1872001
- OpenAlex
- W2166112009
- Cited by
- 165
- References
- 0
- Citations by year
- 2026: 6 · 2025: 3 · 2024: 3 · 2023: 8 · 2022: 3 · 2021: 7 · 2020: 6 · 2019: 7 · 2018: 7 · 2017: 6 · 2016: 6 · 2015: 11 · 2014: 10 · 2013: 14 · 2012: 7
- FWCI
- 2.58
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Neuro-Oncology (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Own your potential (DEAKIN) (submittedVersion)
- Figshare (submittedVersion, cc-by)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
- Health Sciences › Medicine › Genetics › Glioma Diagnosis and Treatment
- Physical Sciences › Materials Science › Polymers and Plastics › Dendrimers and Hyperbranched Polymers
- Keywords
- monocyte-derived dendritic cells, tumor RNA, central nervous system tumors, cancer immunotherapy, tumor-specific immunity, autologous dendritic cell vaccine, leukapheresis, children and young adults
- MeSH terms
- Adolescent, Adult, Antibodies, Neoplasm, Brain Neoplasms, Child, Dendritic Cells, Female, Humans, Immunity, Cellular, Male, Monocytes, RNA, Neoplasm, Immunotherapy, Adoptive, Interleukin-10, Lymphocyte Count, Statistics, Nonparametric, Cancer Vaccines
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