Dual-targeting immunotherapy of lymphoma: potent cytotoxicity of anti-CD20/CD74 bispecific antibodies in mantle cell and other lymphomas

Neutrophil Elastase Promotes Interleukin-1β Secretion from Human Coronary Endothelium

“…No cytokines were detected in these washes (data not shown). In some experiments, cells were preincubated with NEIII (500 M) (20), caspase-1 inhibitor I (YVAD, 50 M) (8,21), or BAF1 (50 nM) (22) for at least 30 min before the addition of NE. At the end of the incubations, supernatants were collected, and the cells were lysed in ice-cold 1% (v/v) Triton X-100 lysis buffer.…”

Construction and characterization of an anti-CD20 mAb nanocomb with exceptionally excellent lymphoma-suppressing activity

“…Previous 54,55 Moreover, mAbevoked HA of NHL cells can trigger specific intracellular alterations including lysosomal membrane permeabilization, mitochondrial depolarization, and phosphorylation or up/downregulation of proteins related to the apoptotic signal transduction pathways, culminating in PCD. 11,15,24,26,30,31 Given previous publications and our findings, it would be reasonable to attribute the superior PCD-inducing ability of PPRT nanocomb partly to the "cross-cell link"-assisted HA. Further experimental results revealed that both CDC and ADCC can also be synchronously activated with the presence of complement and effector cells.…”

“…7,[10][11][12] Despite the success of US Food and Drug Administration (FDA) approved rituximab (RTX) in patients with B-cell NHLs, considerable room for improved therapeutic index remains. Only about 15% of patients with follicular lymphoma respond to the initial treatment with RTX monotherapy, and the majority of responders become refractory to RTX.…”

The Development of Bispecific Hexavalent Antibodies as a Novel Class of DOCK-AND-LOCKTM (DNLTM) Complexes

“…To identify these HexAbs, we assign each of them a code of X-(Y)-(Y), where X and Y are specific designations given to differentiate the antibodies, with the Fab distinguished from the IgG by enclosing its designation in a parenthesis. The present notation is applicable to denote HexAbs that are either bispecific [36][37][38] or monospecific [58]. As an example, 20-(22)- (22), defines the bsHexAb comprising a divalent anti-CD20 humanized IgG (veltuzumab or hA20) and a pair of dimeric anti-CD22 humanized Fab's (epratuzumab or hLL2).…”

“…The initial proof-of concept was provided by linking a stabilized dimer of Fab specific for one antigen to a monomeric Fab with specificity for a different antigen to generate a bispecific trivalent antibody composed of three stably-tethered Fab-arms [32]. Since then, we have applied the DNL method to develop bispecific hexavalent antibodies (bsHexAbs) by derivatizing a divalent IgG, at the carboxyl termini of either the heavy chain (the C H 3-format), or the light chain (the C k -format), to contain two stabilized dimers of Fab with a different specificity from the IgG [36][37][38][39][40]. In this review, we present archetype examples of bsHexAbs and discuss the notable advantages of the C K -format over the C H 3-format as revealed by preclinical results.…”