A recombinant E. coli vaccine to promote MHC class I-dependent antigen presentation: application to cancer immunotherapy.
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.
Radford
K J
KJ
Cancer Research UK, Molecular Oncology Unit, ICSM at Hammersmith Hospital, London, UK.
Higgins
D E
DE
Pasquini
S
S
Cheadle
E J
EJ
Carta
L
L
Jackson
A M
AM
Lemoine
N R
NR
Vassaux
G
G
D000818:Animals; D017951:Antigen Presentation; D001427:Bacterial Toxins; D022361:Escherichia coli Vaccines / Q000008:administration & dosage* / Q000235:genetics; D005260:Female; D015316:Genetic Therapy / Q000379:methods*; D006360:Heat-Shock Proteins; D006460:Hemolysin Proteins; D015395:Histocompatibility Antigens Class I / Q000276:immunology*; D006825:Hybridomas; D016219:Immunotherapy, Adoptive / Q000379:methods*; D051379:Mice; D008810:Mice, Inbred C57BL; D009369:Neoplasms / Q000276:immunology / Q000628:therapy*; D014407:Tumor Cells, Cultured; D019444:Vaccines, DNA / Q000008:administration & dosage* / Q000235:genetics
D001427:Bacterial Toxins; D022361:Escherichia coli Vaccines; D006360:Heat-Shock Proteins; D006460:Hemolysin Proteins; D015395:Histocompatibility Antigens Class I; D019444:Vaccines, DNA; C038705:hlyA protein, Listeria monocytogenes