Abstract
Bispecific CD20xCD3 IgG antibodies are clinically efficacious but are associated with significant toxicity, especially cytokine release syndrome. IGM-2323 is a novel engineered high-affinity, high-avidity anti-CD20 pentameric IgM antibody, with an anti-CD3 scFv fused to the joining (J) chain. IGM-2323 kills CD20 expressing target cells through T-cell dependent cellular cytotoxicity (TDCC) and complement-dependent cytotoxicity (CDC), with minimal cytokine release. We present preclinical data demonstrating potent B-cell killing by IGM-2323, including normal and malignant B-cells with very low CD20 expression and that are resistant to other CD20-directed antibodies.
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