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

K. J. Radford, D. E. Higgins, S. Pasquini, E. J. Cheadle, L. Carta, A. M. Jackson, N. R. Lemoine, G. Vassaux

    Research output: Contribution to journalArticlepeer-review

    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.
    Original languageEnglish
    Pages (from-to)1455-1463
    Number of pages8
    JournalGene Therapy
    Volume9
    Issue number21
    DOIs
    Publication statusPublished - Nov 2002

    Keywords

    • Cancer antigens
    • Dendritic cells
    • E. coli
    • Listeriolysin-O
    • MHC

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