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Preclinical full-scale evaluation of dendritic cells transfected with autologous tumor-mRNA for melanoma vaccination.

Abstract：

: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.

journal_name

Cancer Gene Ther

journal_title

Cancer gene therapy

authors

Kyte JA,Kvalheim G,Aamdal S,Saebøe-Larssen S,Gaudernack G

doi

10.1038/sj.cgt.7700837

subject

Has Abstract

pub_date

2005-06-01 00:00:00

pages

579-91

issue

6

eissn

0929-1903

issn

1476-5500

pii

7700837

journal_volume

12

pub_type

杂志文章

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