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

Gene Ther. 2002 Nov;9(21):1455-63. doi: 10.1038/sj.gt.3301812.

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 K(b)-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-A(b)-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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigen Presentation
  • Bacterial Toxins*
  • Escherichia coli Vaccines / administration & dosage*
  • Escherichia coli Vaccines / genetics
  • Female
  • Genetic Therapy / methods*
  • Heat-Shock Proteins
  • Hemolysin Proteins
  • Histocompatibility Antigens Class I / immunology*
  • Hybridomas
  • Immunotherapy, Adoptive / methods*
  • Mice
  • Mice, Inbred C57BL
  • Neoplasms / immunology
  • Neoplasms / therapy*
  • Tumor Cells, Cultured
  • Vaccines, DNA / administration & dosage*
  • Vaccines, DNA / genetics

Substances

  • Bacterial Toxins
  • Escherichia coli Vaccines
  • Heat-Shock Proteins
  • Hemolysin Proteins
  • Histocompatibility Antigens Class I
  • Vaccines, DNA
  • hlyA protein, Listeria monocytogenes