“…We have previously noted 20 that one effective approach to converting a type I anti-CD20 mAb to a type II can be achieved by making the type I mAb multivalent, as shown by the HexAb generated from the type I veltuzumab, 20- (20)- (20), which exhibits biologic properties attributable to both type II (eg, weak CDC; negative for calcium mobilization; positive for antiproliferation, apoptosis, and HA) and type I (eg, positive for trafficking to lipid rafts). 20 The strategy to target both CD20 and CD74 with distinct mAbs was reported recently by us in a preclinical study that used a combination of milatuzumab and rituximab plus a crosslinking Ab in MCL lines and primary tumor cells, 17 which showed that the treatment resulted in rapid cell death, generation of ROS, loss of ⌬ m , strong HA, and inhibition of p65 nuclear translocation. The observed cell death was attributed to a nonclassical apoptotic mechanism, because it lacked evidence of autophagy and caspaseactivation but required the participation of actin and lysosomes.…”