Development of oral cancer vaccine using recombinant Bifidobacterium displaying Wilms' tumor 1 protein.

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.

• Authors: Koichi Kitagawa, Tsugumi Oda, Hiroki Saito, Ayame Araki, Reina Gonoi, Katsumi Shigemura, Yoshiko Hashii, Takane Katayama, Masato Fujisawa, Toshiro Shirakawa
• Journal: Cancer immunology, immunotherapy : CII (Cancer Immunol Immunother) Vol. 66 Issue 6 Pg. 787-798 (Jun 2017) ISSN: 1432-0851 [Electronic] Germany
• PMID: 28299466 (Publication Type: Journal Article)

Chemical References

• Cancer Vaccines
• WT1 Proteins

Topics

• Animals
• Bifidobacterium (immunology)
• Cancer Vaccines (administration & dosage, immunology)
• Female
• Immunotherapy
• Mice
• Mice, Inbred C57BL
• Mouth Neoplasms (immunology, metabolism, mortality, therapy)
• Survival Rate
• T-Lymphocytes, Cytotoxic (immunology)
• WT1 Proteins (immunology)