Journal
INTERNATIONAL JOURNAL OF CANCER
Volume 105, Issue 6, Pages 811-819Publisher
WILEY-BLACKWELL
DOI: 10.1002/ijc.11149
Keywords
dendritic cell; E. coli; tumour immunotherapy
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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 (DiCs) 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 monocytederived DiCs (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, MARTI, efficiently deliver the HLA-A2-restricted MARTI(27-35). epitope for processing and presentation on human MoDiCs, suggesting the potential of this system as a novel strategy for human tumour immunotherapy. (C) 2003 Wiley-Liss, Inc.
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