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ADCC The targeting of surface antigens expressed on cancer cells by monoclonal antibodies (mAbs) is a promising therapeutic strategy for many cancer types. ADCC (antibody-dependent cell-mediated cytotoxicity, or antibody-dependent cellular cytotoxicity) is a crucial mechanism underlying targeted antibody-based immunotherapy approaches. ADCC is a process in which effector cells of the immune system kill cancer cells through non-phagocytic mechanisms. Antibody contains two portions, antigen-binding fragment (Fab) portion and fragment crystallizable region (Fc) portion. The Fab portion can bind to the specific antigen presented on the surface of cancer cells, while the Fc portion can interact with effector cells. Thus, antibodies can link effector cells to cancer cells and induce the death of cancer cells.
ADCP Antibody-dependent cellular phagocytosis (ADCP) is also an important mechanism for antibody-based cancer immunotherapy. ADCP is a process by which effector cells with phagocytic potential, such as monocytes and macrophages, play phagocytic function after recognition of opsonized bacteria, viruses, infected cells or any cells targeted by a specific antibody. Similar to ADCC, ADCP is a mechanism of host defense in which the antibody binds its cognate antigen on the target cell through its antigen-binding fragment (Fab) portion and recruits the effector cells to the target with its fragment crystallizable region (Fc) portion. The antibody-opsonized target is then ingested and degraded.
Our Capability
Creative Biogene offers high-quality stable cell lines that can be used in ADCC and ADCP cellular assays. These cells are designed to stably overexpress the receptors which can be recognized by the Fc portion of antibodies, such as CD16a/CD32a/CD32b/CD64. In combination with an NFAT-Luciferase reporter system, it is easy to monitor the intracellular signaling by luminescence detection. Each of our ADCC/ADCP stable cell lines is constructed under rigorous quality control system.
ADCC is a process by which immune cells, such as natural killer (NK) cells, recognize and kill target cells coated with specific antibodies. This mechanism plays a vital role in the immune response against viral infections and tumor cells. On the other hand, ADCP involves the engulfment and destruction of antibody-coated pathogens or cancer cells by phagocytic cells, primarily macrophages. Both ADCC and ADCP are crucial in the elimination of pathogens and abnormal cells from the body.
Figure 1. Mechanism of ADCC (A) and ADCP (B). (Ma B, et al., 2020 and van Erp EA, et al., 2019)
The development of stable cell lines expressing ADCC or ADCP machinery has become a valuable tool in immunotherapy research. These cell lines are engineered to produce specific receptors or effector molecules involved in the ADCC/ADCP process, allowing the immune response to be studied in a controlled environment.
Applications for ADCC/ADCP stable cell lines include:
Case Study 1
Palivizumab effectively blocks respiratory syncytial virus (RSV) infection in vitro. However, virus neutralization assays often ignore Fc region-mediated effects. The neutralizing activity of RSV-specific monoclonal antibodies on cells possessing Fc receptors was studied. Subneutralizing concentrations of antibodies lead to antibody-dependent enhancement of RSV infection in monocytes. In contrast to antibodies directed against other epitopes, neutralization by palivizumab was enhanced in cells with Fc receptors.
Figure 2. The neutralization activity of palivizumab is augmented on Vero cells in the presence of Fc gamma receptors. IC50 of human plasma immunoglobulin (A) and monoclonal antibodies (B–I) were determined in Vero cells and Vero cells that stably express Fc gamma receptor 1a (Vero1a) or Vero cells with Fc gamma receptor 2a (Vero2a). (van Mechelen L, et al., 2016)
Case Study 2
For Fcγ receptors (FcγRs), this clustering is driven by binding to antibodies of different affinities, which in turn bind to multivalent antigens. Interpretation and rational manipulation of immunoglobulin (Ig)G effector function is complicated by this activation mechanism, which includes varying affinities between FcγR species and changes in antigen binding valence. Here, researchers demonstrate that a multivalent receptor-ligand binding model can effectively account for the contribution of IgG-FcγR affinity and immune complex valency.
Figure 3. Human FcγR Binding Changes with FcγR-IgG Pair and Valency. Researchers quantitatively measured receptor abundance in each hFcγR-expressing cell line to account for potential sources of this binding variation. This revealed a 20-fold change in expression of each hFcγR. (Robinett R A, et al., 2018)
Q: What is ADCC and how does it work?
A: ADCC is a process in which the immune system destroys target cells using natural killer (NK) cells, macrophages, and other immune cells. It is mediated by antibodies, primarily immunoglobulin G (IgG), which bind to specific antigens on the target cells. This triggers the release of cytotoxic enzymes and cytokines, resulting in the destruction of the target cells.
Q: What role do monoclonal antibodies play in ADCC-based immunotherapies?
A: Monoclonal antibodies are genetically engineered antibodies designed to recognize and bind to specific targets. In ADCC-based immunotherapies, monoclonal antibodies can be tailored to bind exclusively to antigens found on cancer cells. By administering these antibodies to patients, the immune response against cancer cells can be enhanced, leading to their destruction.
Q: What is ADCP and how does it work?
A: Antibody-Dependent Cellular Phagocytosis (ADCP) serves as a remarkable mechanism employed by our immune system to defend the body against harmful pathogens. Through the collaboration of antibodies and phagocytes, ADCP plays a crucial role in pathogen recognition, clearance, and subsequent immune activation.
Q: What are Fc gamma receptors (FCGRs)?
A: Fc gamma receptors (FcγRs) are a group of cell surface receptors that are particularly found on immune cells, specifically on cells of the innate immune system such as macrophages, dendritic cells, and natural killer cells. These receptors play a crucial role in the recognition and activation of the immune response against pathogens, as well as in normal physiological processes.
Q: What is the structure and classification of FCGR?
A: FCGRs are glycoproteins composed of extracellular domains, transmembrane regions, and cytoplasmic tails. They are divided into several classes based on their structural and functional characteristics. The classes include FcγRI (CD64), FcγRIIA (CD32A), FcγRIIB (CD32B), FcγRIIC (CD32C), FcγRIIIA (CD16A), and FcγRIIIB (CD16B).
| Cat.No. | Product Name | Price |
|---|---|---|
| CSC-RO01139 | Human FCGR1A/NFAT-Luc Stable Cell Line - Jurkat | Inquiry |
| CSC-RO01140 | Human FCGR2A(131H)/NFAT-Luc Stable Cell Line - Jurkat | Inquiry |
| CSC-RO01141 | Human FCGR2A(131R)/NFAT-Luc Stable Cell Line - Jurkat | Inquiry |
| CSC-RO01142 | Human FCGR2B/NFAT-Luc Stable Cell Line - Jurkat | Inquiry |
| CSC-RO01143 | Human FCGR3A(158V)/NFAT-Luc Stable Cell Line - Jurkat | Inquiry |
| CSC-RO01144 | Human FCGR3A(158F)/NFAT-Luc Stable Cell Line - Jurkat | Inquiry |
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