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 |