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Utomilumab
CD137 is a member of the tumor necrosis factor (TNF) receptor family. Its alternative names are ''tumor necrosis factor receptor superfamily member 9'' (TNFRSF9), 4-1BB and ''induced by lymphocyte activation'' (ILA). It is of interest to immunologists as a co-stimulatory immune checkpoint molecule. Expression CD137 is expressed by activated T cells of both the CD4+ and CD8+ lineages. Although it is thought to function mainly in co-stimulating those cell types to support their activation by antigen presenting cells expressing its ligand (CD137L), CD137 is also expressed on dendritic cells, B cells, NK cells, neutrophils and macrophages. Specific effects on cells The best characterized activity of CD137 is its costimulatory activity for activated T cells. Crosslinking of CD137 enhances T cell proliferation, IL-2 secretion, survival and cytolytic activity. Further, it can enhance immune activity to eliminate tumors in mice. Interactions CD137 has been shown to interact with TR ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Utomilumab
CD137 is a member of the tumor necrosis factor (TNF) receptor family. Its alternative names are ''tumor necrosis factor receptor superfamily member 9'' (TNFRSF9), 4-1BB and ''induced by lymphocyte activation'' (ILA). It is of interest to immunologists as a co-stimulatory immune checkpoint molecule. Expression CD137 is expressed by activated T cells of both the CD4+ and CD8+ lineages. Although it is thought to function mainly in co-stimulating those cell types to support their activation by antigen presenting cells expressing its ligand (CD137L), CD137 is also expressed on dendritic cells, B cells, NK cells, neutrophils and macrophages. Specific effects on cells The best characterized activity of CD137 is its costimulatory activity for activated T cells. Crosslinking of CD137 enhances T cell proliferation, IL-2 secretion, survival and cytolytic activity. Further, it can enhance immune activity to eliminate tumors in mice. Interactions CD137 has been shown to interact with TR ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
4-1BB Ligand
Tumor necrosis factor ligand superfamily member 9 also known as 4-1BB ligand or 4-1BBL or CD137L is a protein that in humans is encoded by the TNFSF9 gene. 4-1BBL is a type 2 transmembrane glycoprotein receptor that is found on APCs (antigen presenting cells) and binds to 4-1BB (also known as CD137). The 4-1BB/4-1BBL complex belongs to the TNFR:TNF superfamily, which is expressed on activated T Lymphocytes. Structure of 4-1BB/4-1BBL complex The 4-1BB/4-1BBL complex consists of three monomeric 4-1BBs bound to a trimeric 4-1BBL. Each 4-1BB monomer binds to two 4-1BBLs via cysteine-rich domains (CRDs). The interaction between 4-1BB and the second 4-1BBL is required to stabilize their interactions. The link with 4-1BBL is largely made up of amino acids from the dynamic loops of the CRD2 and the β sheet of CRD3 of 4-1BB, according to a detailed study of the binding between the 4-1BB and 4-1BBL interface. CRD2 amino acids (T61, Q67, and K69) interact with the AA′ loop (Y110 and G ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Tumor Necrosis Factors
The tumor necrosis factor (TNF) superfamily is a protein superfamily of type II transmembrane proteins containing TNF homology domain and forming trimers. Members of this superfamily can be released from the cell membrane by extracellular proteolytic cleavage and function as a cytokine. These proteins are expressed predominantly by immune cells and they regulate diverse cell functions, including immune response and inflammation, but also proliferation, differentiation, apoptosis and embryogenesis. The superfamily contains 19 members that bind to 29 members of TNF receptor superfamily. An occurrence of orthologs in invertebrates hints at ancient origin of this superfamily in evolution. The PROSITE pattern of this superfamily is located in a beta sheet The beta sheet, (β-sheet) (also β-pleated sheet) is a common motif of the regular protein secondary structure. Beta sheets consist of beta strands (β-strands) connected laterally by at least two or three backbone hydrog ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Immune Checkpoint
Immune checkpoints are regulators of the immune system. These pathways are crucial for self-tolerance, which prevents the immune system from attacking cells indiscriminately. However, some cancers can protect themselves from attack by stimulating immune checkpoint targets. Inhibitory checkpoint molecules are targets for cancer immunotherapy due to their potential for use in multiple types of cancers. Currently approved checkpoint inhibitors block CTLA4 and PD-1 and PD-L1. For the related basic science discoveries, James P. Allison and Tasuku Honjo won the Tang Prize in Biopharmaceutical Science and the Nobel Prize in Physiology or Medicine in 2018. Stimulatory checkpoint molecules Four stimulatory checkpoint molecules are members of the tumor necrosis factor (TNF) receptor superfamily—CD27, CD40, OX40, GITR and CD137. Another two stimulatory checkpoint molecules belong to the B7-CD28 superfamily—CD28 itself and ICOS. * CD27: This molecule supports antigen-specific ex ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
T Cells
A T cell is a type of lymphocyte. T cells are one of the important white blood cells of the immune system and play a central role in the adaptive immune response. T cells can be distinguished from other lymphocytes by the presence of a T-cell receptor (TCR) on their cell surface. T cells are born from hematopoietic stem cells, found in the bone marrow. Developing T cells then migrate to the thymus gland to develop (or mature). T cells derive their name from the thymus. After migration to the thymus, the precursor cells mature into several distinct types of T cells. T cell differentiation also continues after they have left the thymus. Groups of specific, differentiated T cell subtypes have a variety of important functions in controlling and shaping the immune response. One of these functions is immune-mediated cell death, and it is carried out by two major subtypes: CD8+ "killer" and CD4+ "helper" T cells. (These are named for the presence of the cell surface proteins CD8 or ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
CD4+ Helper Cells
The T helper cells (Th cells), also known as CD4+ cells or CD4-positive cells, are a type of T cell that play an important role in the adaptive immune system. They aid the activity of other immune cells by releasing cytokines. They are considered essential in B cell antibody class switching, breaking cross-tolerance in dendritic cells, in the activation and growth of cytotoxic T cells, and in maximizing bactericidal activity of phagocytes such as macrophages and neutrophils. CD4+ cells are mature Th cells that express the surface protein CD4. Genetic variation in regulatory elements expressed by CD4+ cells determines susceptibility to a broad class of autoimmune diseases. Structure and function Th cells contain and release cytokines to aid other immune cells. Cytokines are small protein mediators that alter the behavior of target cells that express receptors for those cytokines. These cells help polarize the immune response depending on the nature of the immunological ins ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Cytotoxic T Cell
A cytotoxic T cell (also known as TC, cytotoxic T lymphocyte, CTL, T-killer cell, cytolytic T cell, CD8+ T-cell or killer T cell) is a T lymphocyte (a type of white blood cell) that kills cancer cells, cells that are infected by intracellular pathogens (such as viruses or bacteria), or cells that are damaged in other ways. Most cytotoxic T cells express T-cell receptors (TCRs) that can recognize a specific antigen. An antigen is a molecule capable of stimulating an immune response and is often produced by cancer cells, viruses, bacteria or intracellular signals. Antigens inside a cell are bound to class I MHC molecules, and brought to the surface of the cell by the class I MHC molecule, where they can be recognized by the T cell. If the TCR is specific for that antigen, it binds to the complex of the class I MHC molecule and the antigen, and the T cell destroys the cell. In order for the TCR to bind to the class I MHC molecule, the former must be accompanied by a glycoprotein ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
TRAF2
TNF receptor-associated factor 2 is a protein that in humans is encoded by the ''TRAF2'' gene. Function The protein encoded by this gene is a member of the TNF receptor associated factor (TRAF) protein family. TRAF proteins associate with, and mediate the signal transduction from members of the TNF receptor superfamily. This protein directly interacts with TNF receptors, and forms complexes with other TRAF proteins. TRAF2 is required for TNF-alpha-mediated activation of MAPK8/JNK and NF-κB. The protein complex formed by TRAF2 and TRAF1 interacts with the IAP family members cIAP1 and cIAP2, and functions as a mediator of the anti-apoptotic signals from TNF receptors. The interaction of this protein with TRADD, a TNF receptor associated apoptotic signal transducer, ensures the recruitment of IAPs for the direct inhibition of caspase activation. cIAP1 can ubiquitinate and induce the degradation of this protein, and thus potentiate TNF-induced apoptosis. Multiple alternatively s ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Urelumab
Urelumab (BMS-663513 or anti-4-1BB antibody) is a fully human IgG4 monoclonal antibody developed by Bristol-Myers Squibb for the treatment of cancer and solid tumors. Urelumab targets the extracellular domain of CD137 CD137 is a member of the tumor necrosis factor (TNF) receptor family. Its alternative names are ''tumor necrosis factor receptor superfamily member 9'' (TNFRSF9), 4-1BB and ''induced by lymphocyte activation'' (ILA). It is of interest to immunolog .... It specifically binds to and activates CD137-expressing immune cells, stimulating an immune response, in particular a cytotoxic T cell response, against tumor cells. The first phase I trial began in 2006 and final results were published in 2015. Current clinical trials combine urelumab with chemotherapy (NCT00351325), chemoradiation (NCT00461110), ipilimumab (NCT00803374), rituximab (NCT01775631, NCT02420938), cetuximab (NCT02110082), and elotuzumab (NCT02252263), nivolumab (NCT02253992) for metastatic solid tumors ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Oncology
Oncology is a branch of medicine that deals with the study, treatment, diagnosis and prevention of cancer. A medical professional who practices oncology is an ''oncologist''. The name's etymological origin is the Greek word ὄγκος (''ónkos''), meaning "tumor", "volume" or "mass". Oncology is concerned with: * The diagnosis of any cancer in a person (pathology) * Therapy (e.g. surgery, chemotherapy, radiotherapy and other modalities) * Follow-up of cancer patients after successful treatment * Palliative care of patients with terminal malignancies * Ethical questions surrounding cancer care * Screening efforts: ** of populations, or ** of the relatives of patients (in types of cancer that are thought to have a hereditary basis, such as breast cancer) Diagnosis Medical histories remain an important screening tool: the character of the complaints and nonspecific symptoms (such as fatigue, weight loss, unexplained anemia, fever of unknown origin, paraneoplastic phenome ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
