A team at IGM Biosciences Inc., led by Kevin Hart and Bruce Keyt demonstrate the improved performance of an engineered IgM anti-CD20 antibody to achieve complement-dependent cytotoxic cell killing for B-cell lymphoma over IgG alternatives. Due to the development of resistance to the traditional IgG-based therapies such novel antibody alternatives are required.
The IgM gives better killing rates, over a shorter period and crucially of target cells with lower antigen density and in the presence of complement inhibitory conditions.
To understand the dynamics of cell killing by the respective IgM and IgG therapeutic antibodies, target cells were stained with CellTrace Green ("all cells") and in the presence of DRAQ7 to report the failure of the plasma membrane due to the complement effect. This was achieved in a disposable hemocytometer chamber slide C-Chip (Incyto) under environmental control and recorded using the Lionheart Fx microscope (Biotek, Inc.).
Reference:
Hart, Kevin C., Paul R. Hinton, Marigold Manlusoc, Kevin B. Carlin, Samuel Schneider, Maya F. Kotturi, Ramesh Baliga, and Bruce A. Keyt. "An engineered IgM antibody targeting CD20 has enhanced complement-dependent cytotoxicity compared to an IgG." Experimental Hematology (2025): 105250.
Hart, Kevin C., Paul R. Hinton, Marigold Manlusoc, Kevin B. Carlin, Samuel Schneider, Maya F. Kotturi, Ramesh Baliga, and Bruce A. Keyt. "An engineered IgM antibody targeting CD20 has enhanced complement-dependent cytotoxicity compared to an IgG." Experimental Hematology (2025): 105250.
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