PMID- 15818380
OWN - NLM
STAT- MEDLINE
DCOM- 20050816
LR  - 20201226
IS  - 0929-1903 (Print)
IS  - 0929-1903 (Linking)
VI  - 12
IP  - 6
DP  - 2005 Jun
TI  - Preclinical full-scale evaluation of dendritic cells transfected with autologous 
      tumor-mRNA for melanoma vaccination.
PG  - 579-91
AB  - Most cancer vaccines to date have made use of common tumor antigens or allogenic 
      cancer cell lines. The majority of tumor antigens may, however, be unique 
      patient-specific antigens. Dendritic cells (DCs) are the most potent 
      antigen-presenting cells known. The present report is a full-scale preclinical 
      evaluation of autologous DCs transfected with autologous tumor-mRNA (tDCs) for 
      vaccination in malignant melanoma. By using autologous tumor-mRNA, we intend to 
      make the DCs present a broad spectrum of tumor-associated antigens relevant to 
      each individual patient. Previously, we have described effective methods for 
      mRNA-transfection into DCs by square-wave electroporation and for generating 
      large numbers of DCs. Here, we demonstrate the ability of tDCs, made under 
      full-scale vaccine conditions, to generate in vitro T-cell responses specific for 
      antigens encoded by the transfected tumor-mRNA. T-cell proliferation assays 
      demonstrated tDC-specific responses for all six patients tested. Responses were 
      further studied by IFNgamma ELISPOT and Bioplex cytokine assays (two patients) 
      and by experiments on isolated CD4(+) and CD8(+) T cells, including HLA-blockage 
      (one patient). Moreover, we describe the results of extensive tumor-RNA analysis 
      using Agilent Bioanalyser, a method that we have implemented in the clinical 
      protocol. Based on this preclinical evaluation, a vaccine trial has been started.
FAU - Kyte, Jon A
AU  - Kyte JA
AD  - Section for Immunotherapy, Department of Immunology, Cancer Research Institute, 
      The Norwegian Radium Hospital, University of Oslo, 0310 Oslo, Norway. 
      j.a.kyte@klinmed.uoi.no
FAU - Kvalheim, Gunnar
AU  - Kvalheim G
FAU - Aamdal, Steinar
AU  - Aamdal S
FAU - Saeboe-Larssen, Stein
AU  - Saeboe-Larssen S
FAU - Gaudernack, Gustav
AU  - Gaudernack G
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Cancer Gene Ther
JT  - Cancer gene therapy
JID - 9432230
RN  - 0 (Cancer Vaccines)
RN  - 0 (RNA, Messenger)
RN  - 0 (RNA, Neoplasm)
RN  - 82115-62-6 (Interferon-gamma)
SB  - IM
MH  - Adult
MH  - Aged
MH  - CD4-Positive T-Lymphocytes/immunology
MH  - CD8-Positive T-Lymphocytes/immunology
MH  - Cancer Vaccines/genetics/*immunology
MH  - Dendritic Cells/*immunology
MH  - Humans
MH  - Interferon-gamma/metabolism
MH  - Male
MH  - Melanoma/drug therapy/*immunology
MH  - Middle Aged
MH  - RNA, Messenger/*genetics
MH  - RNA, Neoplasm/*genetics
MH  - Transfection
EDAT- 2005/04/09 09:00
MHDA- 2005/08/17 09:00
CRDT- 2005/04/09 09:00
PHST- 2005/04/09 09:00 [pubmed]
PHST- 2005/08/17 09:00 [medline]
PHST- 2005/04/09 09:00 [entrez]
AID - 7700837 [pii]
AID - 10.1038/sj.cgt.7700837 [doi]
PST - ppublish
SO  - Cancer Gene Ther. 2005 Jun;12(6):579-91. doi: 10.1038/sj.cgt.7700837.