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A recombinant E. coli vaccine to promote MHC class I-dependent antigen presentation: application to cancer immunotherapy

Gene Therapy volume 9, pages 1455–1463 (2002)Cite this article

Abstract

We have examined the potential of recombinant Escherichia coli expressing listeriolysin O (LLO) to deliver tumour antigens to dendritic cells (DCs) for cancer immunotherapy. Using OVA as a model tumour antigen, we have shown in murine DCs that E. coli expressing cytoplasmic LLO and OVA proteins can deliver the OVA Kb-restricted epitope SIINFEKL for MHC class I presentation. In contrast, when E. coli expressing OVA alone were used, MHC class II presentation of the OVA 323-339 I-Ab-restricted peptide was predominant. When injected in vivo, DCs pulsed with E. coli expressing LLO and OVA induced production of cytotoxic T-lymphocytes capable of lysing an OVA-expressing melanoma cell line (B16-OVA) and resulted in suppression of tumour growth following challenge with B16-OVA. Immunisation of mice by direct injection of E. coli LLO/OVA provided a more potent anti-tumour response, resulting in complete protection in 75% of mice. Injection of live bacteria was not necessary as immunisation with paraformaldehyde-fixed E. coli LLO/OVA provided an even stronger anti-tumour response against B16-OVA. Altogether, our data highlight the potential of this system as a novel and efficient strategy for tumour immunotherapy.

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Acknowledgements

This work was supported by Cancer Research UK and ‘Help Hammer Cancer’. We would like to thank Del Watling and Sandra Peak for their assistance with in vivo work.

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Author notes

  1. K J Radford

    Present address: Mater Medical Research Institute, South Brisbane, Australia

Authors and Affiliations

  1. Cancer Research UK, Molecular Oncology Unit, ICSM at Hammersmith Hospital, London, UK

    K J Radford, S Pasquini, L Carta, N R Lemoine & G Vassaux

  2. Cancer Research UK, Cancer Medicine Research Unit, Applied Immunology Group, St James's Hospital, Leeds, UK

    E J Cheadle & A M Jackson

  3. Department of Microbiology and Molecular Genetics, Harvard Medical School, Boston, MA, USA

    D E Higgins

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  1. K J Radford
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  2. D E Higgins
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Radford, K., Higgins, D., Pasquini, S. et al. A recombinant E. coli vaccine to promote MHC class I-dependent antigen presentation: application to cancer immunotherapy. Gene Ther 9, 1455–1463 (2002). https://doi.org/10.1038/sj.gt.3301812

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  • DOI: https://doi.org/10.1038/sj.gt.3301812

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