Recombinant antibodies are one of the fastest-growing classes of biotherapeutics in the past two decades. Antibody-dependent cellular cytotoxicity (ADCC) exhibits certain mechanisms of action to treat certain tumors. ADCC enhancement is, now, a very promising approach to improve the efficacy of therapeutic antibody drugs. Creative Biolabs provides a comprehensive list of therapeutic antibodies with enhanced ADCC property to help accelerate your research process.
Because ADCC elicits cell-mediated immune defense, it is now revolutionizing the field of cancer immunotherapy. Through Fab antigen-specific binding, the Fc portion mediates immune recruitment signal. The process starts when Fc binds to certain receptors (FcR) on the surface of effector cells (such as NK cells, neutrophils, γδ T cells, DC, and macrophages). Then, Fc-FcR cross-linking triggers the formation of immune synapses, leading to tumor cell apoptosis through blockage on the binding sites of pro-survival ligands or inhibits the dimerization of the signal receptor.
Fig.1 Antibody-dependent cellular cytotoxicity (from wiki).
Mobilizing ADCC effectors' functions and their roles on tumor elimination have been carefully studied in many preclinical and clinical studies using different therapeutic antibodies. For example, in two preclinical in vivo studies, therapeutic antibodies were observed to show lower anti-tumor activity in FcγR chain-deficient mice, compared with wild-type mice. One clinical study has shown that for patients with metastatic breast cancer who were treated with trastuzumab and taxane, patients with high-affinity FcγRIIIa alleles have a higher response rate than patients with low-affinity alleles. These observations suggest the enhancement of ADCC through the innate immune system may represent a promising approach in the development of therapeutic drugs for tumor studies.
Increasing preclinical and clinical evidence on ADCC lets scientists focus on boosting antibodies bindings to FcγRIIIa. Based on this, Creative Biolabs has developed the afucosylated platform for the production of ADCC enhanced antibodies. Our afucosylated platform uses a CHO cell line in which FUT8 has been knocked out, and which produces antibodies with little to no fucose in the Fc region. The antibody expressed by our afucosylated platform shows enhanced ADCC activity, and is anticipated to have a clinical advantage owing to increased specific lysis of target cells, such as cancer cells, which mediated by Fc receptors present on natural killer cells, macrophages, and other immune cell types.
Fig. 2 The effect of non-fucosylated and fucosylated therapeutic antibodies in inducing ADCC.[1]
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