An Fc engineering approach that modulates antibody-dependent cytokine release without altering cell-killing functions
<p>This research article investigates an Fc engineering approach for monoclonal antibodies (mAbs) that modulates antibody-dependent cytokine release (ADCR) without altering cell-killing functions. IgG1 mAbs elicited robust ADCC (antibody-dependent cell-mediated cytotoxicity) and ADCR of proinflammatory cytokines like IFNγ, IL-1α, and IL-1β from peripheral blood mononuclear cells (PBMCs). In contrast, IgG2 and IgG4 mAbs had limited ability to elicit these responses.</p>
<p>Macrophage-mediated ADCP (antibody-dependent cellular phagocytosis) was elicited by IgG1, IgG2 and IgG4 mAbs. However, IgG1 and IgG4 also induced high levels of anti-inflammatory cytokine IL-10 and other cytokines like IL-8, MIP-1α, MIP-1β, and TNF. IgG2 induced ADCP but minimal cytokine release.</p>
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