Previously, we constructed a recombinant Bifidobacterium longum displaying a partial mouse Wilms' tumor 1 (WT1) protein (B. longum 420) as an oral cancer vaccine using a bacterial vector and demonstrated that oral administration of B. longum 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 Â 10 9 colony-forming units of B. longum 420 induced significantly higher cytotoxicity against TRAMP-C2 cells than intraperitoneal injection of 100 mg of Db126, and the in vivo antitumor activity of B. longum 420 in the TRAMP-C2 tumor model could be augmented by intraperitoneal injections of 250 mg of anti-PD-1 antibody. For the clinical development, we produced the B440 pharmaceutical formulation, which is lyophilized powder of inactivated B. longum 440 displaying the partially modified human WT1 protein. We confirmed that B. longum 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 B. longum 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.

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Soybean plant growth during reproductive stage controls strongly seed yield. Two field experiments were conducted to analyze whether water condition improve soybean plant growth from flowering to the beginning of seed developing stage and which growth factors were related. One experiment was the comparison in plant growth between 2008, a wetter season, and 2009, a drier season. Crop growth rate (CGR) from flowering to beginning seed stage in 2008 was higher than that of 2009 and this was associated with higher mean leaf area index (LAI). Relative growth rate (RGR) in 2008 was as high as that of 2009 and this was associated with higher mean specific leaf area (SLA) in spite of lower net assimilation rate (NAR. The other was the irrigation experiment where we irrigated a half of experimental field during emergence to maturity. Although the differences between the treatments were smaller, CGR, LAI and mean SLA increased by irrigation. These results indicate that the improvement of soil water condition increased CGR with the increase in LAI and keep RGR by high SLA in spite of high total dry weight at flowering and lower NAR during reproductive stage.

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Leaflet inclination angle before paraheliotropism controls seed production of soybean plants. We examined the effect of water condition on the inclination angle of leaflets and petioles of two soybean cultivars. Angles measured in the morning were larger in 2008, a wetter season, than in 2009, a drier season. Angles were similarly larger in irrigated plants than in unirrigated plants. The imposition of drought stress on plants grown in pots reduced these angles with the decline in water content of these tissues. There were significant correlations between inclination angle and water content in leaflets and petioles of plants grown both in the field and in pots. These results indicate that water condition controls leaflet and petiole inclination.