Monoclonal antibodies (mAbs) play an important role in the treatment of different diseases including various tumors, and autoimmune and infectious diseases. They specifically inactivate pathogens and agents of disease thus revolutionising modern medicine. What are mAbs, and how do they develop and function in humans? This article reviews the development of mAbs, their mechanism of action, and their medical application.
What Are Monoclonal Antibodies?
Known as monoclonal antibodies, they are created in the laboratory where molecules produced by a single cell clone – known as a single antibody – bind to a given target, usually a protein on the surface of the cell or pathogen. These molecules are so-called as the antibodies comprising each product are identical, or monoclonal, derived from an individual precursor cell.
a. Structure of Monoclonal Antibodies
Monoclonal antibodies are Y-shaped molecules composed of:
- Two Heavy Chains: The Y-shaped arms with great length, serve to bind the Y to the target antigen.
- Two Light Chains: The shorter arms of the Y, help stabilize the structure.
- Fc Region: The sharp end of the Y, which allows the antibody to interact with the rest of the immune system and bring about a response.
How Are Monoclonal Antibodies Made?
The production of monoclonal antibodies involves several key steps:
a. Immunization
First, the antigen of interest (often a mouse) is immunized with the target antigen to so-called adsorb the immune system to the antigen. That is, the antibodies will be produced against a wide variety of target antigens.
b. Cell Fusion
B cells from the immunized animal were then fused with myeloma (cancer) cells – a hybridoma is created from these two cell types, bringing together the capacity of B cells to produce the specific antibody with the capacity of myeloma cells to grow indefinitely.
c. Screening and Selection
The hybridomas are then screened to identify one that produces the desired antibody; the selected hybridomas are then cloned to produce large quantities of uniform antibodies.
d. Antibody Purification
This involves harvesting the antibodies from the culture medium in which the hybridomas grow so that the final product is pure and contains only the selected monoclonal antibody.
How Do Monoclonal Antibodies Work?
Monoclonal antibodies and antigens are produced by the same organism but have different functions – antibodies prevent harmful entities like cells and pathogens, while antigens initiate specific defenses against these entities. The below table outlines how the monoclonal antibodies work:
a. Binding to Antigens
Since the repeating units in such large molecules can bind to their target antigen very specifically, that helps ensure the accurate prediction of form.
b. Neutralization
In the context of infectious disease, monoclonal antibodies can neutralize pathogens by adhering to them and preventing them from entering or impacting host cells, and this is especially useful against viral infections.
c. Antibody-Dependent Cellular Cytotoxicity (ADCC)
During an ADCC, the Fc part of the monoclonal antibody binds to immune cells such as natural killer (NK) cells, which are then induced to kill the target cells that the antibody is binding to.
d. Complement-Dependent Cytotoxicity (CDC)
Monoclonal antibodies can also act by activating complement – a cascade of proteins in the blood that, once triggered, will bring about the demise of the appropriate target cell. The binding of the antibody to the antigen triggers complement, leading to the formation of a membrane attack complex that lyses the target cell.
e. Direct Antitumor Effects
Monoclonal antibodies could be directed to locate cancer cells for induction of cell death by a process called apoptosis. Other monoclonal antibodies may be attached to a cytotoxic drug or a radioactive substance for likewise toxic cancer-cell targeting.
Applications of Monoclonal Antibodies
Monoclonal antibodies have a broad range of applications in medicine:
a. Cancer Treatment
Targeted Therapy: the immune system products called monoclonal antibodies can very precisely attack cancer cells without major impact on normal cells — for example, trastuzumab (Herceptin) for HER2-positive breast cancer and rituximab (Rituxan) for non-Hodgkin lymphomas.
b. Infectious Diseases
Viral infections represent one of the most common applications of monoclonal antibodies. For instance, treatments or prophylactics have been developed against various viral infections, including COVID-19, where casirivimab and imdevimab (REGEN-COV) have received an Emergency Use Authorization (EUA) for the treatment of mild to moderate COVID-19 in patients at high risk for disease progression. Additionally, these antibodies can help prevent serious symptoms in people exposed to the virus.
c. Autoimmune Disorders
Immune Modulation: For example, Ertelipagh is a monoclonal antibody used in autoimmune diseases, given once a week or once a month by subcutaneous injection or a thirty-millimeter intramuscular injection. adalimumab (Humira) is used in rheumatoid arthritis and other autoimmune conditions.
d. Transplantation
Organ-Rejection Prevention: Following transplantation, transplant recipients are given monoclonal antibodies that inhibit the activation of specific immune cells, such as basiliximab (Simulect) or muromonab-CD3 (Orthoclone OkT3).
Advantages of Monoclonal Antibodies
Monoclonal antibodies offer several advantages over traditional therapies:
- Specificity: They target specific antigens, minimizing off-target effects and reducing potential side effects.
- Consistency: Being produced from a single clone, they provide consistent and reproducible results.
- Generalisability: they can be engineered to bind to almost any target, hence they can be widely applied to more diseases.
Challenges and Future Directions
Despite their benefits, monoclonal antibodies face several challenges:
a. High Costs
The expense of making and manufacturing monoclonal antibodies is prohibitive.
b. Resistance and Efficacy
Antibody resistance is a potential issue, so new versions of this treatment will have to be developed over time. We also need to increase the effectiveness of these treatments – an effort that continues today.
c. Immune Reactions
These include patients who are mounting an anti-lymphocyte immune response against the monoclonal antibodies that have been administered to them, either due to the failure of the antibodies to fully quell their autoimmune reaction, resulting in ‘incomplete’ responses or because the monoclonal antibodies are somehow causing their form of collateral damage.
d. Ongoing Research
Ongoing research, meanwhile, looks to enhance monoclonal antibodies, including creating bispecific antibodies that can bind to two separate targets and boosting antibody efficacy and precision.
monoclonal antibodies were a disruptive force in modern medicine. As a result, they revolutionized treatment options for several diseases, establishing an entirely new paradigm of highly effective and targeted drug delivery. Today, monoclonal antibody-based drugs generate hundreds of billions of dollars in sales annually and, in addition, help millions of patients worldwide. In this essay, we will outline the development of monoclonal antibodies to reveal their place in the modern medical landscape. Furthermore, looking ahead, monoclonal antibodies are set to remain crucial for treating diseases and improving patient outcomes.
