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841P IGM-2323 is a CD20xCD3 IgM Bispecific T-cell Engager That Kills Low CD20-expressing and Rituximab-Resistant B-cell Lymphomas

K. Li, M. F. Kotturi, M. Manlusoc, R. Yun, P. R. Hinton, K. Logronio,R. Baliga,G. Hernandez, A. M. Sinclair, S. F. Carroll,W. R. Godfrey, B. A. Keyt

Annals of oncology(2021)

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摘要
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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