Document Detail


Phase I/II trial of melanoma therapy with dendritic cells transfected with autologous tumor-mRNA.
MedLine Citation:
PMID:  16710345     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
We have developed an individualized melanoma vaccine based on transfection of autologous dendritic cells (DCs) with autologous tumor-mRNA. Dendritic cells loaded with complete tumor-mRNA may generate an immune response against a broad repertoire of antigens, including unique patient-specific antigens. The purpose of the present phase I/II trial was to evaluate the feasibility and safety of the vaccine, and the ability of the DCs to elicit T-cell responses in melanoma patients. Further, we compared intradermal (i.d.) and intranodal (i.n.) vaccine administration. Twenty-two patients with advanced malignant melanoma were included, each receiving four weekly vaccines. Monocyte-derived DCs were transfected with tumor-mRNA by electroporation, matured and cryopreserved. We obtained successful vaccine production for all patients elected. No serious adverse effects were observed. A vaccine-specific immune response was demonstrated in 9/19 patients evaluable by T-cell assays (T-cell proliferation/interferon-gamma ELISPOT) and in 8/18 patients evaluable by delayed-type hypersensitivity (DTH) reaction. The response was demonstrated in 7/10 patients vaccinated intradermally and in 3/12 patients vaccinated intranodally. We conclude that immuno-gene-therapy with the described DC-vaccine is feasible and safe, and that the vaccine can elicit in vivo T-cell responses against antigens encoded by the transfected tumor-mRNA. The response rates do not suggest an advantage in applying i.n. vaccination.
Authors:
J A Kyte; L Mu; S Aamdal; G Kvalheim; S Dueland; M Hauser; H P Gullestad; T Ryder; K Lislerud; H Hammerstad; G Gaudernack
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Publication Detail:
Type:  Clinical Trial, Phase I; Clinical Trial, Phase II; Journal Article; Research Support, Non-U.S. Gov't     Date:  2006-05-05
Journal Detail:
Title:  Cancer gene therapy     Volume:  13     ISSN:  0929-1903     ISO Abbreviation:  Cancer Gene Ther.     Publication Date:  2006 Oct 
Date Detail:
Created Date:  2006-09-13     Completed Date:  2006-11-21     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9432230     Medline TA:  Cancer Gene Ther     Country:  England    
Other Details:
Languages:  eng     Pagination:  905-18     Citation Subset:  IM    
Affiliation:
Section for Immunotherapy, Department of Immunology, Cancer Research Institute, The Norwegian Radium Hospital, University of Oslo, Oslo, Norway. j.a.kyte@klinmed.uio.no
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MeSH Terms
Descriptor/Qualifier:
Adult
Aged
Animals
Cancer Vaccines / administration & dosage*,  adverse effects
Cell Transplantation*
Dendritic Cells*
Dogs
Electroporation
Enzyme-Linked Immunosorbent Assay
Humans
Hypersensitivity, Delayed
Immunity, Cellular
Melanoma / immunology,  therapy*
Middle Aged
RNA, Messenger / genetics*
T-Lymphocytes / immunology
Transfection*
Chemical
Reg. No./Substance:
0/Cancer Vaccines; 0/RNA, Messenger

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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