Human Anti-M2 Monoclonal Antibody (mAb) & ADCC

Background

The human anti-M2 monoclonal antibody (mAb) is a type of monoclonal antibody designed to target a specific antigen known as M2 antigen. The M2 antigen is usually expressed on the surface of certain cancer cells, such as colorectal cancer. Monoclonal antibodies like anti-M2 are engineered to bind specifically to this antigen, which can help in the targeted destruction of cancer cells.

One mechanism through which monoclonal antibodies can exert their anticancer effects is through ADCC, which stands for Antibody-Dependent Cellular Cytotoxicity. ADCC involves the binding of antibodies to the surface of target cells, such as cancer cells, followed by the recruitment of immune cells, particularly natural killer (NK) cells. NK cells possess receptors that can recognize the constant region of antibodies (Fc region) bound to target cells. Upon recognition, NK cells release cytotoxic molecules such as perforin and granzyme, which induce apoptosis (programmed cell death) in the target cells.

In the context of the human anti-M2 monoclonal antibody, ADCC may play a crucial role in the destruction of M2 antigen-expressing cancer cells. By binding to the M2 antigen on cancer cells, the antibody can facilitate the engagement of NK cells, leading to the targeted killing of these cancer cells through ADCC.

Research Results

Human mAb recognizes M2e and induces NK cell-mediated ADCC.
Fig.1 Human Anti-M2 mAb recognizes M2e and induces NK cell-mediated ADCC.1,2	First, this study examines whether M2e binds to mAb and M2-293FT cells. The results showed that mAb binds to M2-293FT. M2e can also be recognized by the mouse anti-M2 14C2 mAb (Fig.1 A). Second, the expression of M2 in A549 cells was tested. The results showed that mAb recognized M2 expressed on the surface of influenza-infected cells (Fig.1 B).
Human mAb induces NK cell-mediated ADCC.
Fig.2 Human Anti-M2 mAb induces NK cell-mediated ADCC.1,2	mAb was added to the cytotoxicity assay. The results showed that the killing of 293FT cells was not affected, but the specific lysis of M2-293FT cells was significantly increased (Fig.2 A). In addition, this study demonstrated the potential of mAb to induce NK cell-mediated ADCC against A549 influenza-infected cells (Fig.2 B).
mAb-induced increased cytokine and chemokine secretion by freshly isolated NK cells.
Fig.3 Anti-M2 mAb-induced increased cytokine and chemokine secretion by freshly isolated NK cells.1,2	The secretion of the chemokines RANTES, MIP-1α, and MIP-β was significantly increased (Fig.3).
Cytokine-preactivated NK cells also exhibit increased mAb-mediated ADCC.1
Fig.4 Cytokine-preactivated NK cells also exhibit increased Anti-M2 mAb-mediated ADCC.1,2	The presence of mAb induces increased killing of M2-293FT cells compared to M2-293FT cell killing without mAb and 293FT cells (Fig.4).

Conclusion

In summary, this study showed the effect of mAb-mediated NK cells on M2-expressing cells in ADCC. In addition, other cell types, such as macrophages and neutrophils, also play a role in ADCC and can be further investigated.

References

1. Simhadri, V.R.; et al. "A human anti-M2 antibody mediates antibody-dependent cell-mediated cytotoxicity (ADCC) and cytokine secretion by resting and cytokine-preactivated natural killer (NK) cells." PloS One. (2015) 10,4 e0124677.
2. Distributed under Open Access license CC0 1.0 Universal, without modification.