Antibody-dependent cell-mediated cytotoxicity (abbreviated as ADCC), refers to the FC segment that binds to the FcR on the surface of killer cells (e.g. NK cells, macrophages, etc.), and then mediates the direct killing of target cells by killer cells. Antibodies are capable of both neutralizing the virus and activating "non-neutralizing" functions. The latter include ADCC and complement activation, which are major components of the immune response and play a key role in the efficacy of some vaccines and antibody drugs. The process of ADCC involves two stages, in which infected cells are first recognized by antibodies, and then destroyed by NK cells.

Antibody drugs are the fastest-growing category of biological therapeutics and are being developed for a variety of medical diseases, particularly oncology targeting monoclonal antibodies (mAbs). ADCC is not only the main way for the body to clear cells infected by viruses or other pathogens through antibodies but also one of the key mechanisms by which antibody drugs exert clinical effects.

The first report to calculate cytotoxicity was published in 1968 and involved radiolabeling target cells with 51Cr. However, the reproducibility of 51Cr release assays was not adequate, and they were unable to evaluate the lysis susceptibilities of distinct cell types within the target cell population. Other improved methods for detecting ADCC activity include flow cytometric technique and lactate dehydrogenase (LDH) release approach.

In clinical trials of biological drugs and immunomodulatory drugs, ADCC activity is one of the indicators for in vitro tests. Testing whether antibodies have the biological activity of ADCC, and further analyzing the strength of the biological activity of ADCC, has become a crucial step in the process of antibody drug development and quality control. Therefore, in clinical trials of monoclonal antibodies, the use of an ADCC assay as a stability test is more consistent with the requirements of biological detection and can quantify Fc effector function in the ADCC mechanism of action during drug discovery and development.

According to the data of 2020, the global drug market exceeds 900 billion U.S. dollars, of which antibody drug sales account for 150 billion U.S. dollars. Adalimumab, with global sales of $19.96 billion, continues to dominate the sales of monoclonal antibodies. In addition, there are currently at least 30 monoclonal antibodies approved for the treatment of a variety of diseases, and more than 300 mAbs are in clinical trials. Examples include the breast cancer drug trastuzumab and rituximab. Rituximab is a drug used to treat diseases which show overactive, dysfunctional, or excessive numbers of B cells (e.g. lymphomas).

Robust ADCC assays are not only applicable for assessing mAb quality but also for predicting patient responses. For example, many patients have limited responses to mAb therapy, so there is a great need for antibodies with enhanced clinical efficacy. ADCC assay can help researchers better design and engineer antibodies with enhanced ADCC eliciting properties, thereby improving the prognosis of patients. ADCC assay is widely used as a new gold standard technique for accurately quantifying cell-mediated cytotoxicity and plays a critical role in the design of novel ADCC-enhanced antibodies.

https://adcc.creative-biolabs.com/adcc-antibody-production.htm
https://adcc.creative-biolabs.com/category-adcc-enhanced-biobetters-357.htm

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