Table 1.
Main characteristics of anti-CD37 directed mAbs.
| Agent Tested | Basic Characteristics | Mechanism of Action | Clinical Significance |
|---|---|---|---|
| Otlertuzumab (formerly known as TRU-016) | Humanized anti-CD37 homodimeric monoclonal antibody engineered with the aid of ADAPTIR platform, based on SMIP-016 | Triggers apoptosis dependent upon BIM upregulation in malignant B cells and induces ADCC | Combined administration of otlertuzumab and bendamustine in relapsed CLL patients resulted in 69% overall response. (NCT01188681) [81] |
| Naratuximab emtansine (formerly known as IMGN529) | Humanized anti-CD37 monoclonal antibody conjugated to maytansine-derived microtubule disruptor known as DM1 | Induces DM1 internalization and processes it, leading to DM1 intracellular release, disruption of microtubule assembly, and consequently cell cycle arrest and apoptosis; significant ADCC activity observed in preclinical studies | Under investigation in a clinical trial in relapsed or refractory NHL and CLL (NCT01534715)Orphan Drug status (designation for EU–May 2015, for US–September 2016), phase IIb study in relapsed/refractory DLBCL (NCT02564744) |
| AGS67E | Fully human monoclonal anti-CD37 antibody conjugated to the microtubule-disrupting agent MMAE via a protease-cleavable linker | Induces efficient cytotoxicity, apoptosis, and cell cycle alterations following the release of MMAE in numerous NHL and CLL cell lines and patient-derived samples in vitro [70] | AGS67E is characterized by a favorable safety profile, the results of a clinical trial in patients with r/r lymphoid malignancies are awaited (NCT02175433)AGS67E revealed potent activity in B/T cell malignancies and AML in vitro [74] |
| BI 836826 | Chimeric Fc-engineered anti-CD37 monoclonal antibody with improved ADCC | Induces apoptosis and demonstrates an improved affinity for the Fc-gamma-RIIIa receptor present on natural killer (NK) cells, leading to effective ADCC | BI836826 demonstrated notable efficacy and acceptable tolerability in phase I clinical trial in patients with CLL (NCT01296932) [5] |
| Betalutin (177) Lu-tetulomab | Murine anti-CD37 monoclonal antibody lilotomab (formerly referred to as HH1) conjugated to the beta-emitting isotope lutetium-177 (Lu-177) via the chemical linker DOTA | Efficiently inhibits cell growth with β-radiation that is emitted from the radionuclide | Under investigation in a clinical trial in relapsed or refractory NHL (LYMRIT-37-05, NCT02658968) |
ADCC: antibody-dependent cellular cytoxicity; NHL: non-Hodgkin lymphoma; DLBCL: diffuse large B cell lymphoma; AML: acute myeloid leukemia; MMAE: microtubule-disrupting agent monomethyl auristatin E.