1,25-dihydroxycholecalciferol

Active form of vitamin D

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

1,25-Dihydroxycholecalciferol, also known as calcitriol, is the hormonally active form of vitamin D. It is a secosteroid hormone that plays a crucial role in the regulation of calcium and phosphate metabolism in the body. Calcitriol is produced in the kidneys from its precursor, 25-hydroxycholecalciferol, which is synthesized in the liver from cholecalciferol (vitamin D3).

Biological Function

Calcitriol functions by binding to the vitamin D receptor (VDR), which is present in various tissues throughout the body. This binding initiates a cascade of events that lead to the transcription of specific genes involved in calcium and phosphate homeostasis. The primary actions of calcitriol include:

• Intestinal Absorption of Calcium and Phosphate: Calcitriol increases the absorption of calcium and phosphate from the gastrointestinal tract, which is essential for maintaining adequate levels of these minerals in the blood.

• Bone Resorption: It stimulates the release of calcium from bone by promoting the differentiation and activity of osteoclasts, the cells responsible for bone resorption.

• Renal Reabsorption: Calcitriol enhances the reabsorption of calcium in the kidneys, reducing its excretion in urine.

Synthesis and Regulation

The synthesis of calcitriol is tightly regulated by several factors:

• Parathyroid Hormone (PTH): PTH is a major regulator of calcitriol production. When blood calcium levels are low, PTH is secreted by the parathyroid glands, stimulating the conversion of 25-hydroxycholecalciferol to calcitriol in the kidneys.

• Serum Calcium and Phosphate Levels: High levels of calcium and phosphate in the blood can inhibit the production of calcitriol.

• Fibroblast Growth Factor 23 (FGF23): This hormone, produced by osteocytes in bone, can decrease calcitriol synthesis.

Clinical Significance

Calcitriol is used therapeutically in the treatment of conditions such as:

• Hypocalcemia: Particularly in patients with chronic kidney disease or hypoparathyroidism.
• Osteoporosis: To help maintain bone density.
• Rickets and Osteomalacia: Conditions caused by vitamin D deficiency.

Pharmacokinetics

Calcitriol is administered orally or intravenously. It has a short half-life of approximately 5 to 8 hours and is highly protein-bound in the bloodstream. It is metabolized in the liver and kidneys and excreted primarily via the biliary route.

Also see

• Vitamin D
• Parathyroid hormone
• Calcium metabolism
• Osteoporosis
• Rickets