Based on this structural feature of mabs, we can roughly divide their mechanisms of action into Fab-related and Fc-related mechanisms of action.
As the antigens recognized by monoclonal antibodies have different physiological functions, the corresponding antibodies also have different functions, including neutralization of free protein target molecules and antagonism or activation of cell surface receptors.
1.Recognize Free Molecular Targets
Cytokines, growth factors, biotoxins and viruses that exist free in the blood circulation can be used as the targets of monoclonal antibodies. Protein factors regulate the function of cells by binding to receptors and transmitting signals into cells. The mechanism of action of neutralizing antibodies is to neutralize the antigen by binding to the antigen, so that the antigen loses the ability to bind to the receptor, and then loses its biological function.
Examples: Bevacizumab, Infliximab, Adalimumab, Raxibacumab
2.Recognize Cell-surface Receptors
Each antibody can specifically bind to a specific antigenic target. The target antigen is expressed on a specific cell surface and has a specific function, such as cell activation, growth, or migration. According to the Fab activity of the antibody, the interaction between the antibody and its target receptor can be divided into binding, antagonism, and activation. Most of the targets that are recognized and bound by antibodies are tumor-associated antigens, which are growth factor receptors that are overexpressed by many malignant tumors. Either antibody inhibits cell growth, induces apoptosis, and arrests the cell cycle by binding to its receptor, affecting its function, and interfering with signal transduction.
Examples: Cetuximab, Panitumumab, Trastuzumab, Rituximab
The Fc region of a monoclonal antibody determines the effector functions of the antibody, including antibody-dependent cellular cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC). ADCC is triggered by FC interaction with FyRIa while CDC is triggered by Fc interaction with a range of complement system components in blood.
1.Antibody-dependent cellular cytotoxicity (ADCC)
When the antibody binds to the surface antigen of tumor cells through the antigen-binding site, and the Fc site binds to the Fc receptor on the surface of immune effector cells, the immune effector cells are activated and kill the tumor target cells. This process is called ADCC. The strength of ADCC mediated by monoclonal antibodies is related to many factors. In general, the closer the binding between tumor target cells and immune effector cells through antibody bridging, the stronger the ADCC effect.
2.Complement-dependent Cytotoxicity (CDC)
Different types of antibodies has different ability to inspire the CDC. Complement is a group of heat-labile, enzymically active proteins present in the serum and tissue fluids of humans or vertebrates. The main function of the complement system is to damage the cell membrane or regulate the surface of pathogens for macrophages to swallow by acting on the surface of pathogens and other targets. In addition, it can also cause inflammatory responses.
In addition to directly interfering with the biological functions of antigens by binding to target antigens and mediating immune responses such as ADCC and CDC through Fc fragments, monoclonal antibodies can also cause adaptive immune responses. It includes cellular immunity such as the activation of tumor antigen-specific cytotoxic T cells and helper T cells, and humoral immunity such as the production of protective antibodies against tumor antigens.