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- W4362493160 abstract "<div>Abstract<p>Previously, we constructed a recombinant <i>Bifidobacterium longum</i> displaying a partial mouse Wilms' tumor 1 (WT1) protein (<i>B. longum</i> 420) as an oral cancer vaccine using a bacterial vector and demonstrated that oral administration of <i>B. longum</i> 420 significantly inhibited tumor growth compared with the Db126 WT1 peptide vaccine in the TRAMP-C2, mouse castration-resistant prostate cancer (CRPC) syngeneic tumor model. The present study demonstrated that oral administration of 1.0×10<sup>9</sup> colony-forming units of <i>B. longum</i> 420 induced significantly higher cytotoxicity against TRAMP-C2 cells than intraperitoneal injection of 100 μg of Db126, and the <i>in vivo</i> antitumor activity of <i>B. longum</i> 420 in the TRAMP-C2 tumor model could be augmented by intraperitoneal injections of 250 μg of anti–PD-1 antibody. For the clinical development, we produced the B440 pharmaceutical formulation, which is lyophilized powder of inactivated <i>B. longum</i> 440 displaying the partially modified human WT1 protein. We confirmed that <i>B. longum</i> 440 could induce cellular immunity specific to multiple WT1 epitopes. In a preclinical dosage study, B440 significantly inhibited growth of the TRAMP-C2 tumors compared with that of the control groups (PBS and <i>B. longum</i> not expressing WT1) at all dosages (1, 5, and 10 mg/body of B440). These mouse doses were considered to correspond with practical oral administration doses of 0.2, 1, and 2 g/body for humans. Taken together, these results suggest that the B440 WT1 oral cancer vaccine can be developed as a novel oral immuno-oncology drug to treat CRPC as a monotherapy or as an adjunct to immune checkpoint inhibitors.</p></div>" @default.
- W4362493160 created "2023-04-05" @default.
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- W4362493160 date "2023-04-03" @default.
- W4362493160 modified "2023-10-01" @default.
- W4362493160 title "Data from Preclinical Development of a WT1 Oral Cancer Vaccine Using a Bacterial Vector to Treat Castration-Resistant Prostate Cancer" @default.
- W4362493160 doi "https://doi.org/10.1158/1535-7163.c.6538372.v1" @default.
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