3e)
3e). exhibited potent target-dependent cytotoxicity against polySia-positive tumor cells and and induced quick internalization of polySia into endosomal and lysosomal compartments. In light of these findings, we hypothesized that this antibody-induced endocytosis of polySia-receptors could be efficiently harnessed as part of an antitumor therapeutic strategy. To test this notion, we designed an ADC using a bioorthogonal reaction plan for stably linking the chimeric human ch735 mAb to the microtubule-inhibitory agent maytansinoid DM1, which has previously been developed as the cytotoxic Rabbit polyclonal to PITPNM2 payload in trastuzumab emtansine (T-DM1) for HER2-positive breast malignancy (27). The producing conjugate was found to exert potent target-dependent cytotoxicity against polySia-positive tumor cells = 3). (b) Time course of antibody internalization in polySia-positive cell collection SH-SY5Y treated with ch735 or isotype control. Data reported as…