Chimeric Monoclonal Antibody

The field of medicine is continually developing through extensive research into what causes diseases in humans and how to prevent and combat these diseases. Today, a significant area of this research is the study of antibodies. An antibody is an immunoglobin (lg), a Y-shaped protein that is manufactured by immune systems to combat pathogens and prevent them from harming the human body.

As expected, further research has emerged to strengthen the immune system against specific and general pathogens. Among these antibodies is the chimeric monoclonal antibody, which has excellent relevance to immunoassays and therapeutic purposes.

In understanding the concept, it is necessary to make recourse to its two components, namely “Chimeric Antibody” and “Monoclonal Antibodies.”

A chimeric antibody is one that is composed of domains from diverse species. On the other hand, monoclonal antibodies are antibodies made by like immune cells, all of which are clones of a rare parent cell. Also, unlike polyclonal antibodies that are capable of binding to various epitopes, monoclonal only binds to a similar epitope. (Larry, 2004)

From the preceding, a chimeric monoclonal antibody is a structural chimera made by integrating variable sectors from a species with the constant region of another specie. For instance, when a human component is combined to replace the Fc area of a mouse mAb. (Kurosawa et al., 2014)

Similarly, this antibody is a medicinal biological agent comprising murine variable fields. In essence, these regions target a given antigen as well as the human FcIg elements. This, in turn, lessens the antibody ‘s immunogenicity while increasing the serum’s half-life. (Kurosawa et al., 2014)

Furthermore, while researchers continue changing the constant area from one specie unto another, including switching subtypes within similar species, this procedure is not straightforward as it appears. It involves some form of genetic engineering. Noteworthy, it generally consists of the joining of a human immunoglobin (Ig) constant sector to the Ig variable area of an identified mouse hybridoma.

Generally, chimeric monoclonal antibodies are particularly crucial and potent both in therapeutics and immunoassays.

Concerning its relevance to in vivo biotherapeutic research, these various monoclonal antibodies have therapeutic effects that, when chimerized, limit immunogenicity among humans. Similarly, they are mostly cheaper than completely humanized antibodies. As such, they play an instrumental role, especially at its early stages, in biotherapeutics research. (Larry, 2004)

In the same vein, it is also relevant to biotherapy and immunoassay in vitro. For instance, its application to immunoassay enabled the significant reduction of background staining following the switching of antibodies to constant regions in a bid to match the host’s species. (Kurosawa et al., 2014)

Similarly, it is also applicable to oncology. This is evident by the chemical antibody – Cetuximab – which comprised of C225, a chimeric molecule that showed an affinity almost five times higher than parental mouse antibodies. It also recorded an increased reduction in tumor growth than parental mouse antibodies. (Kurosawa et al., 2014)

Notably, these chimeric monoclonal antibodies also survived some drawbacks of early murine monoclonal antibodies, making it more useful for therapeutic purposes. For instance, the antibody – Dinutuximab – has an ADCC that is 50 to 100-fold higher than parental mouse antibodies when its application involves human effector cells. As such, it had an improved effector capacity that enables it to function effectively. (Kurosawa et al., 2014)

Applications of a Chimeric Monoclonal Antibody in a Rhesus Monkey

This is a brief report of Shandong et al.’s study on how the antibody works. Noteworthy, in his experiment, he utilized the MHCSZ-123, an example of a chimeric monoclonal antibody.

Background: SZ-123, an example of murine monoclonal antibodies that target the VWF A3 domain in humans. It is a potent antithrombotic and obstructs the collagen from binding. Shandong et al. applied it to a Rhesus Monkey, which is a thrombosis model. They discovered that the SZ-123 had no impact on this Rhesus monkey, and there were no side defects such as bleeding and thrombocytopenia.

Methods: The methods used was to develop the mouse/human chimeric type SZ-123, MHCSZ-123. The type helped to maintain inhibitory capacities within and outside the monkeys after injections. Shandong et al. choose the CHO-S cells for the stable articulation of MHCSZ-123. They also filtered the cell clones of significant degrees of MHCSZ-123 articulation with G41.8. They then adjusted to a culture of serum-free suspension.

Then they observed the antithrombotic impact of MHCSZ-123 on intense platelet-mediated thrombosis in monkeys. Noteworthy, these were monkeys in which clots arrangement was stimulated by injury and by stenosis of the femoral vein. This led to decreases in the cyclic flow. Also, Shandong et al. estimated the CFRs in the femoral arteries of anesthetized Rhesus monkeys before and after they admitted the intravenous MHCSZ-123.

Outside the body, Shandong et al. measured antithrombotic activity by platelet counts. Bleeding time of template and binding of VWF to collagen were also part of the measurements. Finally, they measured the occupancy of VWF, as well as VWF by ELISA.

Results: Injecting 0.1 mg/kg of MHCSZ-123 reduced the CFR’s by 29.4%. Injection of 0.3 mg/kg mg/kg of MHCSZ-123 reduced CFR by 57.9%. Injection of 0.6 mg/kg of MHCSZ-123 reduced CFR by 73.1%

More, they observed a 46.6% - 65.8% inhibitions of platelet aggression as induced by ristocetin. Noteworthy, they made this observation between 15 and 30 min after injection.

Shandong et al. also observed minimal outcomes regarding bleeding time. Also, the blood loss was minimal. There were zero cases of uncontrolled bleeding called thrombocytopenia.

From the findings, the VWF-A3 inhibitor MHCSZ-123, a chimeric monoclonal, substantially minimized the Rhesus monkey’s thrombosis. It also seemed safe.

Without a doubt, the development of this antibody has gone a long way in strengthening medical resistance to pathogens among humans. This is because it provides a unique and precise approach that researchers can tailor towards specific targets. Even more, they avoid the drawbacks associated with the orthodox approach. Needless to say, it also significantly aids in vivo and in vitro research and diagnostic assay’s development.