RRC ID 50821
著者 Kitagawa K, Oda T, Saito H, Araki A, Gonoi R, Shigemura K, Hashii Y, Katayama T, Fujisawa M, Shirakawa T.
タイトル Development of oral cancer vaccine using recombinant Bifidobacterium displaying Wilms' tumor 1 protein.
ジャーナル Cancer Immunol Immunother
Abstract Several types of vaccine-delivering tumor-associated antigens (TAAs) have been developed in basic and clinical research. Wilms' tumor 1 (WT1), identified as a gene responsible for pediatric renal neoplasm, is one of the most promising TAA for cancer immunotherapy. Peptide and dendritic cell-based WT1 cancer vaccines showed some therapeutic efficacy in clinical and pre-clinical studies but as yet no oral WT1 vaccine can be administrated in a simple and easy way. In the present study, we constructed a novel oral cancer vaccine using a recombinant Bifidobacterium longum displaying WT1 protein. B. longum 420 was orally administered into mice inoculated with WT1-expressing tumor cells for 4 weeks to examine anti-tumor effects. To analyze the WT1-specific cellular immune responses to oral B. longum 420, mice splenocytes were isolated and cytokine production and cytotoxic activities were determined. Oral administrations of B. longum 420 significantly inhibited WT1-expressing tumor growth and prolonged survival in mice. Immunohistochemical study and immunological assays revealed that B. longum 420 substantially induced tumor infiltration of CD4+T and CD8+T cells, systemic WT1-specific cytokine production, and cytotoxic activity mediated by WT1-epitope specific cytotoxic T lymphocytes, with no apparent adverse effects. Our novel oral cancer vaccine safely induced WT1-specific cellular immunity via activation of the gut mucosal immune system and achieved therapeutic efficacy with several practical advantages over existing non-oral vaccines.
巻・号 66(6)
ページ 787-798
公開日 2017-6-1
DOI 10.1007/s00262-017-1984-0
PII 10.1007/s00262-017-1984-0
PMID 28299466
MeSH Animals Bifidobacterium / immunology* Cancer Vaccines / administration & dosage* Cancer Vaccines / immunology Female Immunotherapy* Mice Mice, Inbred C57BL Mouth Neoplasms / immunology* Mouth Neoplasms / metabolism Mouth Neoplasms / mortality Mouth Neoplasms / therapy* Survival Rate T-Lymphocytes, Cytotoxic / immunology WT1 Proteins / immunology*
IF 5.442
引用数 9
リソース情報
一般微生物 JCM 31944