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Phase I/II trial of a dendritic cell vaccine transfected with DNA encoding melan A and gp100 for patients with metastatic melanoma
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Steele, J. C., Rao, A., Marsden, J. R., Armstrong, C. J., Berhane, S., Billingham, L. J., Graham, N., Roberts, C., Ryan, G., Uppal, H., Walker, C., Young, Lawrence S. and Steven, N. M. (2011) Phase I/II trial of a dendritic cell vaccine transfected with DNA encoding melan A and gp100 for patients with metastatic melanoma. Gene Therapy, Vol.18 (No.6). pp. 584-593. doi:10.1038/gt.2011.1
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Official URL: http://dx.doi.org/10.1038/gt.2011.1
Abstract
This trial tested a dendritic cell (DC) therapeutic cancer vaccine in which antigen is loaded using a novel non-viral transfection method enabling the uptake of plasmid DNA condensed with a cationic peptide. Proof of principle required the demonstration of diverse T lymphocyte responses following vaccination, including multiple reactivities restricted through both major histocompatibility complex (MHC) class I and II. Patients with advanced melanoma were offered four cycles of vaccination with autologous DC expressing melan A and gp100. Disease response was measured using Response Evaluation Criteria in Solid Tumours. Circulating MHC class I- and II-restricted responses were measured against peptide and whole antigen targets using interferon-γ ELIspot and enzyme-linked immunosorbent assay assays, respectively. Responses were analyzed across the trial population and presented descriptively for some individuals. Twenty-five patients received at least one cycle. Vaccination was well tolerated. Three patients had reduction in disease volume. Across the trial population, vaccination resulted in an expansion of effector responses to both antigens, to the human leukocyte antigen A2-restricted modified epitope, melan A ELAGIGILTV, and to a panel of MHC class I- and II-restricted epitopes. Vaccination with mature DC non-virally transfected with DNA encoding antigen had biological effect causing tumour regression and inducing diverse T lymphocyte responses.
| Item Type: | Journal Article | ||||
|---|---|---|---|---|---|
| Divisions: | Faculty of Medicine > Warwick Medical School | ||||
| Journal or Publication Title: | Gene Therapy | ||||
| Publisher: | Nature Publishing Group | ||||
| ISSN: | 0969-7128 | ||||
| Official Date: | June 2011 | ||||
| Dates: |
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| Volume: | Vol.18 | ||||
| Number: | No.6 | ||||
| Page Range: | pp. 584-593 | ||||
| DOI: | 10.1038/gt.2011.1 | ||||
| Status: | Peer Reviewed | ||||
| Publication Status: | Published | ||||
| Access rights to Published version: | Restricted or Subscription Access |
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