Indeed, inhibition of the ubiquitin pathway results in increased Nectin2 surface expression and enhances tumor cell susceptibility to NK cell cytotoxicity.
In addition, the expression levels of Nectin-2 protein in ESCC tissues with advanced tumor stage (P=0.006) and poor differentiation (P=0.02) were increased compared with patients with early tumor stage and well to moderate differentiation.
Furthermore, we discovered multiple anti-Nectin-2 fully human monoclonal antibodies which inhibited tumor growth in in vivo subcutaneous xenograft models with antibody-dependent cellular cytotoxicity (ADCC) as the principal mechanism of action.
Results showed that the percentage of positive Nectin-2 and DDX3 expression was significantly higher in PDAC tumors than in peritumoral tissues, benign pancreatic tissues, and normal pancreatic tissues (P < 0.01).
We expressed, purified and confirmed the identity of recombinant sCD226 (19aa-248aa) and then examined the effect of sCD226 on tumor cell growth using CD226 ligand (CD155 and CD112)-expressing cancer cell lines (K562, HeLa).
These results suggest that modulation of the expression of receptors and CD112 compensates for CD155 deficiency in immune surveillance against MCA-induced tumors.
In addition, we tested anti-Nectin-2 mAbs in several in vivo tumor growth inhibition models to investigate the primary mechanisms of action of the mAbs.