Thanks to cellular biology and biotechnology advances, mAbs has opened a new window of opportunities in clinical practice.
Schematic Structure of a mAb
All immunoglobulins are composed of two identical heavy chains linked by disulphide bonds and two identical light chains. The Fab region contains the antigen binding site at the end of the two arms of the Y-shaped molecule. Complementary-determining regions (CDRs) dictate the precise antigen-binding characteristics of the antibody. It is composed of three short polypeptide segments on the heavy chain and three on the light chain. The site of interaction with the complement system is found on the Fc domain and its receptors determine the fate of the bound antigen.
Mechanism of Action with Antiviral Properties
- Receptor engagement is blocked through binding of the antibody to a specific virus surface protein (Tocilizumab).
- Viral infection neutralization can be done through conformational changes interference that are require for membrane fusion.
- mAbs may prevent the release of progeny virions
- Neutralization inside the endosomes for the viruses that requires an endocytosis
Mechanism of Action with Therapeutic mAbs
Antibody-dependent cell-mediated cytotoxicity (ADCC):the target cell expresses a specific antigen where the Fv binding domain of the antibody binds. This will then recruit immune-effector cells such as macrophages and natural killer (NK) cells which will lyse the target cell.
Complement-dependent cytotoxicity (CDC): When triggered, CDC activates a cascade of complement proteins which forms the antibody-antigen complex to attack the membrane that kills the target cell.
Antibody-dependent cellular phagocytosis (ADCP): It connects its Fc domain to specific receptors on phagocytic cells and thus eliciting phagocytosis.
Complement component 1q (C1q): This the first subcomponent of the C1 complex that serves as a recognition and regulatory protein for the proteolytic complement cascade.
Drug delivery carrier: Antibodies can be drug delivery carriers when conjugated to drugs, radioisotopes, toxins, or cytokines. This type of action uses the specificity of mAbs to deliver the said examples to deliver successfully to antigen-expressing cells.
It is essential that the drug delivering antibody has a high specificity, high affinity, and has the capability to induce receptor mediated internalization. In the structure, the mAb should act as a targeting agent.