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Enhancing ADCC Efficacy of an Anticancer mAb Therapeutic

Increasing afucosylation % of a monoclonal antibody by optimizing process parameters can enhance the efficacy of anticancer antibody therapeutics.

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Released By Bora Biologics

The poster describes how to enhance antibody-dependent cellular cytotoxicity (ADCC) of an anticancer monoclonal antibody overexpressed in Chinese hamster ovary (CHO) cells through cell culture process optimization to increase the afucosylated glycan population. The antibody is a monoclonal humanized IgG1 isotype that selectively binds to the extracellular receptor of cancer cells to induce antibody-dependent cellular cytotoxicity, leading to the death of cells that express the cancer target. The mechanism of action of the therapeutical antibody is in part related to ADCC. Afucosylated antibodies lacking the core fucose residue from Fc N-glycans exhibit strong ADCC at lower concentrations with much higher efficacy compared to fucosylated counterparts and can evade the inhibitory effect of serum immunoglobulin G (IgG) on ADCC through high binding to gamma receptor IIIa (FcγRIIIa). We enhanced the ADCC effect by increasing the % of afucosylated species through optimization of the cell culture process using a design of experiments (DOE) approach.

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