Anti-lymphocyte Globulin
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Anti-lymphocyte Globulin
Anti-lymphocyte globulin (ALG) is an infusion of animal- antibodies against human T cells which is used in the treatment of acute rejection in organ transplantation. Its use was first reported by Thomas Starzl in 1966. Its use in transplant was supplanted by thymoglobulin between 1984 and 1999. It has also been used in the treatment of aplastic anemia. It is less commonly used than the similar anti-thymocyte globulin (ATG), and like ATG it is associated with cytokine release syndrome in the short term and an increased risk of post-transplant lymphoproliferative disorder in the long term. ALG is more likely to cause side effects than ATG, but is safer than OKT3. The product was manufactured by Upjohn The Upjohn Company was a pharmaceutical manufacturing firm founded in 1886 in Hastings, Michigan, by Dr. William E. Upjohn who was an 1875 graduate of the University of Michigan medical school. The company was originally formed to make ''friabl ... and Merieux, as well as the ...
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Infusion
Infusion is the process of extracting chemical compounds or flavors from plant material in a solvent such as water, oil or alcohol, by allowing the material to remain suspended in the solvent over time (a process often called steeping). An infusion is also the name for the resultant liquid. The process of infusion is distinct from both decoction—a method of extraction involving boiling the plant material—and percolation, in which water is passed through the material (as in a coffeemaker). History The first recorded use of essential oils was in the 10th or 11th century by the Persian polymath Avicenna, possibly in ''The Canon of Medicine''. Tea is far older than this, dating back to the 10th century BC as the earliest recorded reference. Preparation techniques Infusion is a chemical process that uses botanicals (typically dried herbs, flowers or berries) that are volatile and release their active ingredients readily in water, oil, or alcohol. In this process, a liquid i ...
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Anti-thymocyte Globulin
Anti-thymocyte globulin (ATG) is an infusion of horse or rabbit-derived antibodies against human T cells and their precursors (thymocytes), which is used in the prevention and treatment of Transplant rejection, acute rejection in organ transplantation and therapy of aplastic anemia due to bone marrow insufficiency. Uses Two antithymocyte globulin (ATG) agents licensed for clinical use in the United States are Thymoglobulin (rabbit ATG, rATG, Genzyme) and Atgam (equine ATG, eATG, Pfizer). Thymoglobulin and Atgam are currently licensed for use in the treatment of renal allograft rejection; Atgam is additionally licensed for use in the treatment of aplastic anemia. Both drugs are used in off-label applications, especially as immunosuppression induction agents before and/or during kidney transplantation. A rabbit anti-T lymphocyte globulin made by Neovii Pharmaceuticals is marketed outside of the United States under the name Grafalon. ATG administration very substantially reduces imm ...
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Upjohn
The Upjohn Company was a pharmaceutical manufacturing firm founded in 1886 in Hastings, Michigan, by Dr. William E. Upjohn who was an 1875 graduate of the University of Michigan medical school. The company was originally formed to make ''friable pills'', which were specifically designed to be easily digested. These could be "reduced to a powder under the thumb", a strong marketing argument at the time. History Upjohn developed a process for the large scale production of cortisone. The oxygen atom at the 11 position in this steroid is an absolute requirement for biological activity. There are however no known natural sources for starting materials that contain that feature. The only method for preparing this drug prior to 1952 was a lengthy synthesis starting from cholic acid isolated from bile. In 1952, two Upjohn biochemists, Dury Peterson and Herb Murray announced that they were able to introduce this crucial oxygen atom by fermentation of the steroid progesterone with a comm ...
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OKT3
Muromonab-CD3 (trade name Orthoclone OKT3, marketed by Janssen-Cilag) is an immunosuppressant drug given to reduce acute rejection in patients with organ transplants. It is a monoclonal antibody targeted at the CD3 receptor, a membrane protein on the surface of T cells. It was the first monoclonal antibody to be approved for clinical use in humans. History Muromonab-CD3 was approved by the U.S. Food and Drug Administration (FDA) in 1986, making it the first monoclonal antibody to be approved anywhere as a drug for humans. In the European Communities, it was the first drug to be approved under the directive 87/22/EWG, a precursor of the European Medicines Agency (EMEA) centralised approval system in the European Union. This process included an assessment by the Committee for Proprietary Medicinal Products (CPMP, now CHMP), and a subsequent approval by the national health agencies; in Germany, for example, in 1988 by the Paul Ehrlich Institute in Frankfurt. However, the manufacture ...
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Adverse Effect (medicine)
An adverse effect is an undesired harmful effect resulting from a medication or other intervention, such as surgery. An adverse effect may be termed a "side effect", when judged to be secondary to a main or therapeutic effect. The term complication is similar to adverse effect, but the latter is typically used in pharmacological contexts, or when the negative effect is expected or common. If the negative effect results from an unsuitable or incorrect dosage or procedure, this is called a medical error and not an adverse effect. Adverse effects are sometimes referred to as "iatrogenic" because they are generated by a physician/treatment. Some adverse effects occur only when starting, increasing or discontinuing a treatment. Adverse effects can also be caused by placebo treatments (in which case the adverse effects are referred to as nocebo effects). Using a drug or other medical intervention which is contraindicated may increase the risk of adverse effects. Adverse effects may c ...
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Post-transplant Lymphoproliferative Disorder
Post-transplant lymphoproliferative disorder (PTLD) is the name given to a B cell proliferation due to therapeutic immunosuppression after organ transplantation. These patients may develop infectious mononucleosis-like lesions or polyclonal polymorphic B-cell hyperplasia. Some of these B cells may undergo mutations which will render them malignant, giving rise to a lymphoma. In some patients, the malignant cell clone can become the dominant proliferating cell type, leading to frank lymphoma, a group of B cell lymphomas occurring in immunosuppressed patients following organ transplant. Signs and symptoms Symptoms of PTLD are highly variable and nonspecific, and may include fever, weight loss, night sweats, and fatigue. Symptoms may be similar to those seen in infectious mononucleosis (caused by EBV). Pain or discomfort may result from lymphadenopathy or mass effect from growing tumors. Dysfunction may occur in organs affected by PTLD. Lung or heart involvement may result in shortne ...
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Cytokine Release Syndrome
Cytokine release syndrome (CRS) is a form of systemic inflammatory response syndrome (SIRS) that can be triggered by a variety of factors such as infections and certain drugs. It refers to cytokine storm syndromes (CSS) and occurs when large numbers of white blood cells are activated and release inflammatory cytokines, which in turn activate yet more white blood cells. CRS is also an adverse effect of some monoclonal antibody medications, as well as adoptive T-cell therapies. When occurring as a result of a medication, it is also known as an infusion reaction. The term cytokine storm is often used interchangeably with CRS but, despite the fact that they have similar clinical phenotype, their characteristics are different. When occurring as a result of a therapy, CRS symptoms may be delayed until days or weeks after treatment. Immediate-onset CRS is a cytokine storm, although severe cases of CRS have also been called cytokine storms. Signs and symptoms Symptoms include fever th ...
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Aplastic Anemia
Aplastic anemia is a cancer in which the body fails to make blood cells in sufficient numbers. Blood cells are produced in the bone marrow by stem cells that reside there. Aplastic anemia causes a deficiency of all blood cell types: red blood cells, white blood cells, and platelets. It occurs most frequently in people in their teens and twenties but is also common among the elderly. It can be caused by heredity, immune disease, or exposure to chemicals, drugs, or radiation. However, in about half of cases, the cause is unknown. Aplastic anemia can be definitively diagnosed by bone marrow biopsy. Normal bone marrow has 30–70% blood stem cells, but in aplastic anemia, these cells are mostly gone and are replaced by fat. First-line treatment for aplastic anemia consists of immunosuppressive drugs—typically either anti-lymphocyte globulin or anti-thymocyte globulin—combined with corticosteroids, chemotherapy, and ciclosporin. Hematopoietic stem cell transplantation is a ...
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Antibody
An antibody (Ab), also known as an immunoglobulin (Ig), is a large, Y-shaped protein used by the immune system to identify and neutralize foreign objects such as pathogenic bacteria and viruses. The antibody recognizes a unique molecule of the pathogen, called an antigen. Each tip of the "Y" of an antibody contains a paratope (analogous to a lock) that is specific for one particular epitope (analogous to a key) on an antigen, allowing these two structures to bind together with precision. Using this binding mechanism, an antibody can ''tag'' a microbe or an infected cell for attack by other parts of the immune system, or can neutralize it directly (for example, by blocking a part of a virus that is essential for its invasion). To allow the immune system to recognize millions of different antigens, the antigen-binding sites at both tips of the antibody come in an equally wide variety. In contrast, the remainder of the antibody is relatively constant. It only occurs in a few varia ...
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Thymoglobulin
Thymoglobulin (manufactured by Sanofi) is an anti-human thymocyte immunoglobulin preparation made of purified polyclonal antibodies derived from rabbits. While these antibodies have a variety of specificities, their main mechanism of immunosuppression is through depletion of T cells. Thymoglobulin is currently approved for clinical use in Europe and the United States for renal allograft rejection, prevention of graft-vs.-host disease, and conditions involving bone marrow failure, including aplastic anemia and has additional off-label uses. History of antithymocyte globulin Antithymocyte globulin (ATG) was originally developed as one of various tested preparations of antilymphocyte globulin (ALG) specifically generated against human lymphocytes within the thymus, or thymocyte A Thymocyte is an immune cell present in the thymus, before it undergoes transformation into a T cell. Thymocytes are produced as stem cells in the bone marrow and reach the thymus via the blood. Thymopoiesi ...
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Thomas Starzl
Thomas Earl Starzl (March 11, 1926 – March 4, 2017) was an American physician, researcher, and expert on organ transplants. He performed the first human liver transplants, and has often been referred to as "the father of modern transplantation." A documentary, entitled "Burden of Genius," covering the medical and scientific advances spearheaded by Starzl himself, was released to the public in 2017 in a series of screenings. Dr. Starzl also penned his autobiography, "The Puzzle People: Memoirs Of A Transplant Surgeon," which was published in 1992. Life Early years Starzl was born on March 11, 1926, in Le Mars, Iowa, the son of newspaper editor and science fiction writer Roman Frederick Starzl and Anna Laura Fitzgerald who was a teacher and a nurse. He was the second of four siblings. Originally intending to become a priest in his teenage years, Starzl changed his plans drastically when his mother died from breast cancer in 1947. Education He attended Westminster Co ...
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