Triparanol

A synthetic cholesterol-lowering drug

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

Triparanol was a cholesterol-lowering drug that was developed in the 1950s and marketed in the early 1960s. It was withdrawn from the market due to adverse effects.

History

Triparanol was introduced as a cholesterol-lowering agent in the early 1960s. It was marketed under the brand name MER/29. The drug was one of the first synthetic agents used to lower cholesterol levels in the blood.

Mechanism of Action

Triparanol works by inhibiting the enzyme desmosterol _24-reductase, which is involved in the biosynthesis of cholesterol. This inhibition leads to the accumulation of desmosterol, a precursor in the cholesterol synthesis pathway, and a reduction in cholesterol levels.

Adverse Effects

Despite its effectiveness in lowering cholesterol, Triparanol was associated with several adverse effects. Patients reported side effects such as cataracts, alopecia, and skin disorders. These adverse effects were significant enough to lead to the withdrawal of the drug from the market.

Withdrawal from the Market

Due to the severe side effects, Triparanol was withdrawn from the market in 1962. The withdrawal highlighted the importance of thorough drug testing and monitoring for adverse effects.

Legacy

The case of Triparanol is often cited in discussions about drug safety and the importance of post-marketing surveillance. It serves as a reminder of the potential risks associated with new pharmaceuticals and the need for rigorous clinical trials.

Related pages

• Cholesterol
• Desmosterol
• Drug safety

Triparanol

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