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.
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.
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).
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.
Indeed, inhibition of the ubiquitin pathway results in increased Nectin2 surface expression and enhances tumor cell susceptibility to NK cell cytotoxicity.