An Overview of Monoclonal Antibodies and its Applications

Antibodies or immunoglobulins (Ig) are glycoproteins generated by differentiated B lymphocytes called plasma cells in response to susceptibility to antigens. The diversity of antibody responses to various target antigens is because of the gene recombination process in the hyper-variable areas of antibodies. 

Throughout the recombination technique in their genes, antibodies experience gene rearrangement that enables them for various binding. Antibodies’ tremendous specificity and diversity have made them notable molecules with increased efficiencies in several therapeutic or diagnostic applications. The polyclonal antibody, monoclonal antibody and recombinant secondary antibody, as well as antibody fragments, can be used for western blotting. Polyclonal secondary antibodies are the most common form of secondary antibodies ab 2 fragments in use.

Monoclonal antibodies (mAbs) are produced by identical clones of B lymphocytes against a particular antigen. mAbs are similar in several properties such as protein sequence, antigen-binding site region, binding affinity for their targets, and identical downstream functional effects.

Monoclonal antibodies (mAbs) are commonly administered via the subcutaneous (SC) route. However, bioavailability is often reduced after SC administration. In addition, the sequential transfer of mAbs through the SC tissue and lymphatic system is not entirely understood.  

According to the immune response’s heavy chain constant region, distribution, and function, Monoclonal antibodies can be classified into different classes or isotypes. Mammalians have five different antibodies, including 

• IgG, 
• IgM, 
• IgD, 
• IgA, and 
• IgE. 

The IgG is the most appropriate and abundant type from those antibody isotypes because it plays a vital role in the immune response. For this cause, most antibodies used in research, therapy, and diagnostics are IgG immunoglobulins.

While both polyclonal and monoclonal antibodies have a vital role in biomedical research, in this article we explore the uses and applications of Monoclonal antibodies. For further reading on the uses and applications of polyclonal antibodies, please see our previous article. 

Therapeutic and Diagnostic Applications of MAbs 

Given their importance as reagents, the clinical uses of monoclonal antibodies are plenty. Due to their selectivity, specificity, high binding affinity, and immunogenicity/low toxicity, monoclonal antibodies are suitable for clinical, environmental, elemental research and more. The application of monoclonal antibodies is commonly observed in therapeutics and diagnostics, including medical devices, vitro tests, and medical imaging. 

Through therapeutic applications, monoclonal antibodies can be used in their naked form or as carriers by being conjugated to a tiny molecule or drug. While performing diagnostic and research applications, monoclonal antibodies are often conjugated with fluorescent tags for visual detection of targets or enzymes.

1. MAbs in Biochemical Analysis

Symptomatic tests based on MAbs are reagents that are routinely used in radioimmunoassay (RIA) and enzyme-linked immunosorbent assays (ELISA) in labs. Those assays estimate the circulating concentrations of hormones like insulin, human chorionic gonadotropin, growth hormone, progesterone, thyroxine, triiodothyronine, thyroid-stimulating hormone, and several other tissue and cell products. In current years, various diagnostic kits using MAbs have grown to be commercially available. Now it is helpful for diagnosis of different diseases:

• In Pregnancy: Pregnancy by indirect detection of the urinary levels of human chorionic gonadotropin.
• In Cancers: Cancers estimation of plasma carcinoembryonic antigen in colorectal cancer and prostate-specific antigen for prostate cancerous cell. Besides diagnosis, evaluation of tumour markers is also essential for the diagnosis of cancers. A constant fall in specific tumour antigens is observed with a contraction in tumour size following treatment. 
• In Hormonal disorders: Hormonal dysfunctions analysis of triiodothyronine, thyroxine and thyroid-stimulating hormone for thyroid disorders.

2. Use of MAbs in Therapy against Complications of Viral Infections

Cytomegalovirus (CMV) induces severe immunocompromised illnesses, such as patients with AIDS and those going through organ transplants. Infection frequencies may increase up to 75% in those negative for CMV who receive kidneys from seropositive patients. CMV infection can result in retinitis and gastroenteritis in HIV-infected patients and may also cause chronic pain intrauterine disease. 

About 40,000 cases of congenital CMV infection are recorded each year; mental retardation and hearing loss might occur in around 25% of those cases. Presently, there is no vaccine against CMV. Ganciclovir, foscarnet, and (S)-1-[3-hydroxy-(2 phosphonylmethoxy) procytosine are a few of the possible treatments for Cytomegalovirus infection.

Another method of medication is via regulation of anti-CMV hyper immunoglobulin obtained from combined sera of CMV-seropositive persons. Passive immunisation has been attested to reduce the severity of CMV and block mother-to-infant transference.

Furthermore, humanised antibodies may evacuate the virus from infected tissues, and a purpose earlier thought to be exclusive to cytotoxic T lymphocytes. Many doctors use a blend of antiviral agents and immunoglobulins in patients in danger of CMV infection. MAbs may also reduce the number of antiviral agents needed for treatment. MAbs against murine CMV polypeptides are shielding in animal models.

3. Use of MAb in Cancer: Radioimmunotherapy

Advances in radiolabeling have allowed immuno-conjugates to be delivered to cells and showed promise in clinical trials. Radioimmunotherapy uses a radiolabeled MAb to provide radioactive isotopes in targeted cells. Radioisotopes such as iodine-131 and yttrium-90, which are β emitters, can cause damage not only to the bound cell but also to cells adjacent to tumour cells that humanized antibodies may not be able to reach within the tumours. 

The absence of knowledge about the suitable dose, shedding of target antigen hinders radioisotopes and biodistribution. Radiolabeled MAbs may also attack healthy cells, depending on the degree to which reticuloendothelial cells exposing Fc receptors bind to the connected regions of unimpaired antibody molecules. Using antibody particles or constructs might modify this nonspecific uptake.

4. Use of MAbs in Therapy of Asthma

Enormous levels of IgE might cause bronchial hyperresponsiveness, an uncertainty factor for asthma. Immune responses propitiated by IgE are crucial in the pathogenesis of allergic asthma.

Two two-week injections of recombinant humanised anti-IgE antibodies were performed in a recent study with patients reporting mild to acute allergic asthma.

It forms complexes with unfettered IgE and obstructs its communication with mast cells and basophils, directed to a fall in serum IgE levels and slightly reduced asthma symptom scores compared to the placebo group. Subjects receiving anti-IgE were capable of decreasing dependence on corticosteroids. 

5.Use of MAbs in the treatment of AIDS

Immunosuppression is the hallmark of AIDS, and it is induced by a reduction in cluster determinant antigen 4 (CD4) cells of T-lymphocytes. The HIV or human immunodeficiency virus binds to specific receptors on CD4 cells by using exterior membrane glycoprotein (gp). 

Genetic engineers have been prospering in connecting the Fc portion of rat monoclonal antibodies to human CD4 molecules. This complex has a great affinity to attach to membrane glycoprotein gp120 of virus-infected cells. The Fc remnant induces cell-mediated eradication of HIV infected cells.

6 Use of MAbs in COVID-19 treatment

In May 2021 the FDA issued an emergency use authorization (EUA) for the investigational monoclonal antibody therapy Sotrovimab for the treatment of mild-to-moderate COVID-19 in adults and paediatric patients (12 years and older weighing at least 40 kilograms) with positive results of direct SARS-CoV-2 viral testing and who are at high risk for progression to severe COVID-19, including hospitalisation or death. This includes patients of 65 years of age and older or individuals who have certain medical conditions.

Sotrovimab is a monoclonal antibody that is specifically directed against the spike protein of SARS-CoV-2 and is designed to block the virus’ attachment and entry into human cells. Sotrovimab is not authorised for patients hospitalised due to COVID-19 or those requiring oxygen therapy due to COVID-19.

Conclusion

Immunology has developed at a speedy pace and has produced many critical developments. Although vaccination has thus far been determined to be the most cost-effective method of limiting and preventing diseases universally, the development of MAbs that utilise the specificity of immunological responses is one of the most successful applications of immunology to date. 

Chimeric and humanised antibodies have reduced the risk of allergenicity from exposure to nonself antibodies and heightened the clinical effectiveness of MAb treatments. Advancements in radiology and pharmacology have permitted radiolabeled and immunoconjugate antibodies to be produced. Fab fragments, heteropolymers, and bispecific antibodies are now available in addition to whole MAbs. These assuring advancements may soon allow humanised monoclonal antibodies to be used to treat diseases as varied as lung cancer, asthma, viral infection, septicemia, and poisoning.

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