期刊
GENE THERAPY
卷 9, 期 21, 页码 1455-1463出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/sj.gt.3301812
关键词
dendritic cells; E. coli; listeriolysin-O; cancer antigens; MHC
We have examined the potential of recombinant Escherichia coli expressing listeriolysin 0 (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.
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