生物
MHC I级
细胞毒性T细胞
抗原
免疫疗法
抗原呈递
免疫系统
癌症免疫疗法
主要组织相容性复合体
李斯特菌溶血素O
癌症疫苗
癌症研究
免疫学
表位
CD8型
T细胞
细菌
体外
生物化学
单核细胞增生李斯特菌
李斯特菌
遗传学
作者
Kristen J. Radford,Darren E. Higgins,Susanna Pasquini,Eleanor J. Cheadle,L Carta,Andrew M. Jackson,Nicholas R. Lemoine,Georges Vassaux
出处
期刊:Gene Therapy
[Springer Nature]
日期:2002-10-14
卷期号:9 (21): 1455-1463
被引量:66
标识
DOI:10.1038/sj.gt.3301812
摘要
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.
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