IgG, IgM, IgA, IgE, and IgD are the five most common types of antibodies in the body's immune system, and they protect us from foreign antigens through their different abilities. As one of the most common, IgG is the main component of serum immunoglobulin, accounting for about 75% of its total. At the same time, IgG is also the most durable and important antibody in the primary immune response. IgG antibody is composed of two parts: Fab fragment binds to the target effector cell epitope, and Fc fragment binds to FcR on the surface of killer cells (NK cells and macrophages, etc.), so as to mediate antibody-dependent cellular cytotoxicity (ADCC), antibody-dependent cell phagocytosis cellular phagocytosis (ADCP), and complement-dependent cytotoxicity (CDC) effects.
Fig.1 Schematic diagram of IgG and the three effects. ¹
In the ADCP effect, the IgG antibody molecule binds to the antigen on the cell surface and recruits aggregated macrophages through its Fc fragment. Then the macrophages engulf and digest the tumor cells or germ cells. This process can attack and destroy tumor cells, which is an important mechanism that makes ADCP an important mechanism for antibody drug development.
Fig.2 Simplified schematic diagram of the mechanism of mAb-induced ADCP. ²
ADCP is mediated by multiple effector cells, including macrophages, monocytes, dendritic cells, and neutrophils, through FcγR. When the Fab region of the antibody binds to a specific antigen on the surface of the target cell, the Fc region of the antibody binds to and activates various Fcγ receptors on the effector cells. Activation of specific Fcγ receptors (e.g., FcγRIIa, FcγRI, and FcγRIIIa) leads to the activation of various complex pathways, resulting in phagocytosis and destruction of target cells in the lysosomes of effector cells.
Fig.3 Binding affinity of Fc receptors associated with ADCP. ³
FcγRIIa is the main Fcγ receptor involved in the ADCP process, which is mainly expressed in myeloid effector cells, including neutrophils and macrophages, and plays an important activation role in the ADCP effect.
FcγRIIa exhibits polymorphisms, with higher affinities for the R131H variant and IgG1. On the one hand, the ADCP effect can induce effector cells to directly engulf target cells, and on the other hand, when the ADCP effect is initiated, macrophages and others will present the processed tumor antigen to T cells, thereby initiating long-term tumor-specific immunity. At present, the phagocytic effect of macrophages on tumor cells mediated by the enhancement of Fc-terminal amino acid substitution of antibodies has already been applied to therapeutic antibodies.
There is substantial evidence that ADCP can help prevent or reduce the severity of different types of viral infections. Further research into the role of ADCP in different responses and the specific epitopes targeted by ADCP antibodies may provide insight into rational vaccine design strategies to elicit these types of antibody responses while avoiding deleterious antibody-dependent enhancement activity.
Creative Biolabs has developed easy-to-use, clear, and reproducible ADCP assays, including but not limited to:
If you are interested in our ADCP assay, please do not hesitate to contact us or directly send us a quotation.
Creative Biolabs provides luciferase-based ADCC assay. This Jurkat cell based assay is pioneered by Creative Biolabs, and the methodology is very well accepted by the field. See attached ADCC Reporter Assay Protocol for further details.
All products and services are for Research Use Only. Do Not use in humans.
ADCC Assay WT vs AfucoTM Mabs Visit
Antibody Fc Engineering: Towards Better Therapeutics Visit
Creative Biolabs has established a team of customer support scientists ready to discuss ADCC/CDC optimization strategies, antibody production, bioinformatics analysis and other molecular biology/biotechnology issues.