MOR208 (XmAb® 5574, MOR00208) is a novel Fc-engineered humanized CD19 monoclonal antibody. Compared to unmodified parental CD19 antibody, the introduction of S239D and I332E amino acid substitutions in the Fc region of MOR208 enhances antigen-dependent ADCC and antigen-dependent cell-mediated phagocytosis. MOR208 is currently investigated in clinical trials involving patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL). Phase I dose escalation studies showed that MOR208 was safe and well-tolerated in patients.
MOR208 is originally developed to meet the needs of new therapies calling for an agent with higher activity on CD19-positive cancers. Compared to unmodified parental CD19 antibody, the S239D and I332E amino acid substitutions engineered into the MOR208 IgG1 Fc domain resulted in increased ADCC potency and maximum cytotoxicity than anti-CD19 antibody with the wild-type Fc domain.
Fig.1 Fc-optimized MOR208.
Fc-engineered MOR208 is thought to mediate its therapeutic activity against CD19-positive tumors by:
Fig.2 Mechanisms of action of MOR208.
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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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