Cyclosporin

Engineered Monoclonal Antibodies

Diagram of engineered monoclonal antibodies

Engineered monoclonal antibodies are a class of biological therapies that are designed to target specific antigens on the surface of cells. These antibodies are produced using recombinant DNA technologies and are used in the treatment of various diseases, including cancer, autoimmune disorders, and infectious diseases.

Structure and Function

Monoclonal antibodies are composed of two identical heavy chains and two identical light chains, forming a Y-shaped molecule. The tips of the "Y" contain the antigen-binding sites, which are highly specific to the target antigen. This specificity allows monoclonal antibodies to bind to their target with high affinity, blocking or modulating the function of the antigen.

Types of Engineered Monoclonal Antibodies

There are several types of engineered monoclonal antibodies, each designed for specific therapeutic purposes:

• Chimeric antibodies: These antibodies are composed of murine (mouse) variable regions and human constant regions. They are less immunogenic than fully murine antibodies.

• Humanized antibodies: These antibodies are mostly human, with only the antigen-binding sites derived from murine sources. This reduces the risk of immune reactions.

• Fully human antibodies: These are entirely human in origin, produced using transgenic mice or phage display technologies.

• Bispecific antibodies: These antibodies are engineered to bind two different antigens simultaneously, offering unique therapeutic mechanisms.

Applications in Medicine

Engineered monoclonal antibodies have revolutionized the treatment of many diseases:

• Cancer therapy: Monoclonal antibodies can target specific tumor antigens, leading to direct tumor cell killing or recruitment of immune cells to attack the tumor.

• Autoimmune diseases: By targeting specific components of the immune system, monoclonal antibodies can reduce inflammation and tissue damage in diseases such as rheumatoid arthritis and multiple sclerosis.

• Infectious diseases: Monoclonal antibodies can neutralize pathogens or their toxins, providing passive immunity or enhancing the host's immune response.

Production

The production of engineered monoclonal antibodies involves several steps:

1. Antigen identification: The target antigen is identified and characterized. 2. Hybridoma technology: B cells from immunized animals are fused with myeloma cells to create hybridomas that produce the desired antibody. 3. Recombinant DNA technology: Genes encoding the antibody are cloned and expressed in suitable host cells, such as Chinese hamster ovary cells. 4. Purification and formulation: The antibodies are purified and formulated for clinical use.

Challenges and Future Directions

While engineered monoclonal antibodies have shown great promise, there are challenges such as high production costs, potential for immune reactions, and the development of resistance. Ongoing research aims to improve antibody design, reduce immunogenicity, and enhance therapeutic efficacy.

Related Pages

• Monoclonal antibody therapy
• Biopharmaceutical
• Immunotherapy
• Hybridoma technology

Cyclosporin, also spelled cyclosporine, is an immunosuppressant medication widely used in organ transplantation to prevent rejection. It is a cyclic polypeptide consisting of 11 amino acids and is produced by the fungus *Tolypocladium inflatum*. Cyclosporin has revolutionized transplant medicine since its discovery and introduction into clinical practice.

History

Cyclosporin was discovered in 1971 by Jean-François Borel, a Swiss scientist working for Sandoz (now Novartis). It was first isolated from a soil sample obtained in Norway. The drug was initially investigated for its antifungal properties, but its immunosuppressive effects were soon recognized, leading to its development as a medication to prevent organ rejection.

Mechanism of Action

Cyclosporin works by inhibiting the activity of calcineurin, a protein phosphatase involved in activating T-cells of the immune system. By binding to the cytosolic protein cyclophilin, cyclosporin forms a complex that inhibits calcineurin, thereby preventing the transcription of interleukin-2 (IL-2) and other cytokines essential for T-cell activation and proliferation.

Clinical Uses

Cyclosporin is primarily used to prevent organ rejection in kidney, liver, heart, and other organ transplants. It is also used in the treatment of certain autoimmune disorders, such as rheumatoid arthritis and psoriasis. In ophthalmology, cyclosporin is used in the form of eye drops to treat chronic dry eye disease.

Side Effects

The use of cyclosporin is associated with several side effects, including:

• Nephrotoxicity: Cyclosporin can cause kidney damage, which is dose-dependent and requires careful monitoring of kidney function.
• Hypertension: Patients on cyclosporin often experience elevated blood pressure.
• Hyperlipidemia: Increased levels of cholesterol and triglycerides can occur.
• Gingival hyperplasia: Overgrowth of gum tissue is a common side effect.
• Hirsutism: Excessive hair growth can be seen in some patients.

Drug Interactions

Cyclosporin is metabolized by the cytochrome P450 3A4 enzyme system in the liver. As a result, it can interact with a wide range of drugs, including:

• Antibiotics such as erythromycin and clarithromycin, which can increase cyclosporin levels.
• Antifungal agents like ketoconazole, which can also increase cyclosporin levels.
• Anticonvulsants such as phenytoin and carbamazepine, which can decrease cyclosporin levels.

Monitoring

Patients on cyclosporin require regular monitoring of blood levels to ensure therapeutic efficacy while minimizing toxicity. Kidney function, blood pressure, and lipid levels should also be monitored regularly.

Also see

• Immunosuppressive drug
• Organ transplantation
• Calcineurin inhibitor
• Autoimmune disease

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