In recent years, monoclonal antibody (mAb)-based therapeutics have become one of the fastest growing classes of therapy for human diseases, especially cancers. Most of the therapeutic antibodies induce the death of their target via a mechanism termed antibody-dependent cell mediated cytotoxicity or ADCC.
As always focused on the research spotlight, Creative Biolabs now offers flexible primary ADCC assay services that can be incorporated with other functional assays to provide comprehensive Fc function analysis and characterization, to ensure greater prediction of success for both preclinical and clinical studies.
Since ADCC is a critical mechanism in the anti-cancer activities of many mAbs, increasing ADCC activity is commonly a goal in developing cancer therapies. In vitro ADCC assays using primary effector cells are often performed to assist in the screening of candidate molecules for expected ADCC activity and to provide the biological characterization of the clinical candidates for regulatory filings.
The three basic components of ADCC were identified as antibodies, effector cells, and target cells coated with antigens. The activation of natural killer (NK) surface is included in the typical ADCC. NK cells express Fc receptors, predominantly FcγRIIIa (CD16 or CD16a), on its cell surface. These Fc receptors recognize and bind to the Fc portion of an antibody, such as IgG that can bind to the surface of a target cell expressing tumor, viral, or bacterial antigens. Once the Fc receptor binds to the Fc region of IgG, the NK cell releases cytokines including IFN-γ and cytotoxic molecules that can attack the target cell.
Primary peripheral blood mononuclear cells (PBMCs) and freshly isolated NK cells are most commonly used effector cells for ADCC assays. The differences of these two effector cell sources are that primary PBMCs can be applied to the general characterization of in vitro ADCC activity, while primary NK cells are more suitable for studies where low ADCC activity is expected because of the low antigen density on target cells or low binding affinity of the antibody.
Fig.1 Diverse mechanisms of actions described for antibody-based drugs.1, 3
At Creative Biolabs, everything we do is built around the needs and requirements of our clients all over the world. We’re one of the world-top CROs specialized in drug discovery, with the ability to a matchless range of subject-matter expertise to solve complicated issues. Our scientists have longstanding experience in primary ADCC assays. The results of our primary ADCC assays are accurate and reliable to advance your antibody drug discovery project to the next phase.
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Now, we provide two distinct well-established assay formats for ADCC bioactivity evaluating:
This study highlights the role of NK cells in targeting both stem-like/poorly differentiated tumors and well-differentiated tumors through different mechanisms. While direct cytotoxicity is involved in killing stem-like tumors, antibody-dependent cellular cytotoxicity (ADCC) plays a significant role in eliminating well-differentiated tumors. The use of antibodies targeting specific surface receptors expressed on well-differentiated tumors, such as MICA/B, EGFR (Epidermal growth factor receptor), and PDL1, enhances NK cell-mediated ADCC without the need for direct killing. This discovery sheds light on the promising therapeutic role of NK cells across various types of tumors.
Fig.2 Data showcasing PBMC ADCC assay results for an anti-EGFR (Epidermal growth factor receptor) antibody.2, 3
In addition to ADCC assays, Creative Biolabs also offers the following services regarding Fc-mediated Effector Functional Assays:
If you have any special needs in primary ADCC assays or be interested in learning more about Creative Biolabs’ ADCC assay services, please contact us for more information.
References
For Research Use Only.