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

AbstractSeveral 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 b e administrated in a simple and easy way. In the present study, we constructed a novel oral cancer vaccine using a recombinantBifidobacterium 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 oralB. longum 420, mice splenocytes were isolated and cytokine production and cytotoxic activities were determined. Oral administrations ofB. longum 420 significantly inhibited WT1-expressing tumor growth and prolonged survival in mice. Immunohistochemical study and immunological assays revealed thatB. 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 wit...
Source: Cancer Immunology, Immunotherapy - Category: Cancer & Oncology Source Type: research