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- Title
Recombinant E. coli efficiently delivers antigen and maturation signals to human dendritic cells: Presentation of MART1 to CD8<sup>+</sup> T cells.
- Authors
Kristen J. Radford; Andrew M. Jackson; Jui-Ho Wang; Georges Vassaux; Nicholas R. Lemoine
- Abstract
The generation of tumour-specific cytotoxic T-lymphocyte (CTL) responses is the primary focus in the design of immunotherapeutic cancer vaccines. We have recently demonstrated generation of ovalbumin (OVA)-specific CTLs and tumour-protection in a murine tumour model using vaccination with dendritic cells (DCs) pulsed with E. coli expressing listeriolysin O (LLO) and OVA as a model antigen. In this system paraformaldehyde fixation of E. coli/LLO provided an additional safety feature without compromising vaccine efficacy. We therefore reasoned that paraformaldehyde-fixed recombinant E. coli expressing LLO would be an efficient vehicle for the delivery of human tumour antigens to human DCs. In the present study, we demonstrate that fixed E. coli expressing LLO are taken up efficiently by human monocyte-derived DCs (MoDCs) with minimal toxicity. As a consequence of the interaction with bacteria, human DCs undergo marked phenotypic and functional maturation. Furthermore, we show that fixed E. coli/LLO expressing the well-characterised human melanoma antigen, MART1, efficiently deliver the HLA-A2-restricted MART12735 epitope for processing and presentation on human MoDCs, suggesting the potential of this system as a novel strategy for human tumour immunotherapy. © 2003 Wiley-Liss, Inc.
- Subjects
ESCHERICHIA coli; ANTIGENS; DENDRITIC cells; T cells; CANCER vaccines; CELL-mediated cytotoxicity; IMMUNOTHERAPY; LABORATORY mice
- Publication
International Journal of Cancer, 2003, Vol 105, Issue 6, p811
- ISSN
0020-7136
- Publication type
Article
- DOI
10.1002/ijc.11149