Ublituximab (TG-1101) is a novel glycoengineered monoclonal antibody (mAbs) that targets the B lymphocyte CD20 antigen. Ublituximab was originally developed by TG Therapeutics, Inc. to treat B cell proliferative disorders, including non-Hodgkin's lymphoma (NHL) and chronic lymphocytic leukemia (CLL). It is now also being studied for its role in autoimmune diseases such as Multiple Sclerosis (MS), lupus and rheumatoid arthritis. There is currently Phase 3 clinical study on Ublituximab for patients with hematologic malignancies and MS.
Currently, three engineered anti-CD20 mAbs, Rituximab, ofatumumab and ofatumumab, have been recognized and approved by the Food and Drug Administration. Rituximab is a partially humanized chimeric mAb that has a human Fc portion and also retains a murine variable region that recognizes CD20. Both ofatumumab and ublituximab b are fully humanized mAbs that can reduce unintended immune responses during treatment. Specifically, ublituximab is a type I glycosylation-modified novel mAb containing a low-fucose Fc region that promotes enhanced ADCC activity in vitro, resulting in better binding to immune effector cells.
Fig.2 Three engineered anti-CD20 antibodies.
Like other Type I mAbs, rituximab and orfarizumab, ublituximab induces the formation of CD20 lipid rafts and binding between tetramers, resulting in stronger ADCC and decreased direct cell death (DCD). FYI, type II mAbs do not cause lipid raft formation or significantly activate ADCC. The glycosylated Fc portion of Ublituximab is more potently involved in ADCC and antibody-dependent phagocytosis (ADP) to promote binding and effector cells recruitment, even in those patients with low-affinity Fc gamma polymorphisms.
Fig.3 Mechanisms of action of CD20 mAbs.
Ublituximab exhibits enhanced ADCC activity in lysis assays.
Currently, Ublituximab is being study in Phase 3 clinical development for patients with hematologic malignancies and MS. Combination studies are undergoing for research in multiple B-cell malignancies.
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Creative Biolabs provides luciferase-based ADCC assay. This Jurkat cell based assay is pioneered by Creative Biolabs, and the methodology is very well accepted by the field. See attached ADCC Reporter Assay Protocol for further details.
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