CD27
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CD27
CD27 is a member of the tumor necrosis factor receptor superfamily. It is currently of interest to immunologists as a co-stimulatory immune checkpoint molecule, and is the target of an anti-cancer drug in clinical trials. Expression During mouse embryonic development, specific (medium) expression levels of CD27 (in addition to high KIT (gene), cKit, medium GATA2, Gata2, and high CD31 expression levels) define the very first adult definitive Hematopoietic stem cell, hematopoietic stem cells generated in the aorta-gonad-mesonephros region. Furthermore, CD27 is expressed on both naïve and activated effector T cells as well as Natural killer cell, NK cells and activated B cells. It is a type I transmembrane protein with cysteine-rich domains, but once T cells have become activated, a soluble form of CD27 can be shed. Function The protein encoded by this gene is a member of the TNF-receptor superfamily. This receptor is required for generation and long-term maintenance of T cell ...
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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 ...
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SIVA1
Apoptosis regulatory protein Siva is a protein that in humans is encoded by the ''SIVA1'' gene. This gene encodes a protein with an important role in the apoptotic (programmed cell death) pathway induced by the CD27 antigen, a member of the tumor necrosis factor receptor (TFNR) superfamily. The CD27 antigen cytoplasmic tail binds to the N-terminus of this protein. Two alternatively spliced transcript variants encoding distinct proteins have been described. Interactions SIVA1 has been shown to interact with CD27. Siva (protein) Siva protein is a zinc-containing intracellular ligand of the CD4 receptor that promotes HIV-1 envelope-induced apoptosis in T-lymphoid cells. Recent research has demonstrated that Siva is a direct transcriptional target for the tumor-suppressors p53 and E2F1. See also * Siva (protein) Apoptosis regulatory protein Siva is a protein that in humans is encoded by the ''SIVA1'' gene. This gene encodes a protein with an important role in the apoptotic (prog ...
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Siva (protein)
Apoptosis regulatory protein Siva is a protein that in humans is encoded by the ''SIVA1'' gene. This gene encodes a protein with an important role in the apoptotic (programmed cell death) pathway induced by the CD27 antigen, a member of the tumor necrosis factor receptor (TFNR) superfamily. The CD27 antigen cytoplasmic tail binds to the N-terminus of this protein. Two alternatively spliced transcript variants encoding distinct proteins have been described. Interactions SIVA1 has been shown to interact with CD27. Siva (protein) Siva protein is a zinc-containing intracellular ligand of the CD4 receptor that promotes HIV-1 envelope-induced apoptosis in T-lymphoid cells. Recent research has demonstrated that Siva is a direct transcriptional target for the tumor-suppressors p53 and E2F1. See also * Siva (protein) Apoptosis regulatory protein Siva is a protein that in humans is encoded by the ''SIVA1'' gene. This gene encodes a protein with an important role in the apoptotic (prog ...
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Tumor Necrosis Factor Receptor
The tumor necrosis factor receptor superfamily (TNFRSF) is a protein superfamily of cytokine receptors characterized by the ability to bind tumor necrosis factors (TNFs) via an extracellular cysteine-rich domain. With the exception of nerve growth factor (NGF), all TNFs are homologous to the archetypal TNF-alpha. In their active form, the majority of TNF receptors form trimeric complexes in the plasma membrane. Accordingly, most TNF receptors contain transmembrane domains (TMDs), although some can be cleaved into soluble forms (e.g. TNFR1), and some lack a TMD entirely (e.g. DcR3). In addition, most TNF receptors require specific adaptor protein such as TRADD, TRAF, RIP and FADD for downstream signalling. TNF receptors are primarily involved in apoptosis and inflammation, but they can also take part in other signal transduction pathways, such as proliferation, survival, and differentiation. TNF receptors are expressed in a wide variety of tissues in mammals, especially in leukocy ...
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TNF-receptor Superfamily
The tumor necrosis factor receptor superfamily (TNFRSF) is a protein superfamily of cytokine receptors characterized by the ability to bind tumor necrosis factors (TNFs) via an extracellular cysteine-rich domain. With the exception of nerve growth factor (NGF), all TNFs are homologous to the archetypal TNF-alpha. In their active form, the majority of TNF receptors form trimeric complexes in the plasma membrane. Accordingly, most TNF receptors contain transmembrane domains (TMDs), although some can be cleaved into soluble forms (e.g. TNFR1), and some lack a TMD entirely (e.g. DcR3). In addition, most TNF receptors require specific adaptor protein such as TRADD, TRAF, RIP and FADD for downstream signalling. TNF receptors are primarily involved in apoptosis and inflammation, but they can also take part in other signal transduction pathways, such as proliferation, survival, and differentiation. TNF receptors are expressed in a wide variety of tissues in mammals, especially in leukocy ...
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Varlilumab
Varlilumab (INN; development code CDX-1127) is a monoclonal antibody designed for immunotherapy for solid tumors and hematologic malignancies. It is an anti-CD27 antibody and helps activate T-cells. This drug was developed by Celldex Therapeutics. It (in combination with ONT-10) has undergone a phase 1B clinical trial for advanced breast or ovarian cancer. In combination with anti-PD-1 nivolumab Nivolumab, sold under the brand name Opdivo, is a medication used to treat a number of types of cancer. This includes melanoma, lung cancer, malignant pleural mesothelioma, renal cell carcinoma, Hodgkin lymphoma, head and neck cancer, urotheli ... it has undergone a phase 1/2 trial for advanced refractory solid tumours References {{Cytokine receptor modulators Monoclonal antibodies ...
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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 ...
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CD70
CD70 (Cluster of Differentiation 70) is a protein that in humans is encoded by ''CD70'' gene. CD70 is a ligand for CD27. Clinical significance The CD70 protein is expressed on highly activated lymphocytes (like in T- and B-cell lymphomas). It is therefore suggested that anti-CD70 antibodies might be a possible treatment for CD70 positive lymphomas as normal lymphocytes have low CD70 expression. Drug development ARGX-110 is a CD70-specific antibody that is currently under investigation for the treatment of hematological malignancies. It is being developed by the Belgian company arGEN-X. In December 2013 a first part of a phase 1b trial was completed. In January 2014 a safety and efficacy phase of the study started. Vorsetuzumab mafodotin is a CD70-targeted antibody-drug conjugate that started clinical trials for renal cell carcinoma. See also * Cluster of differentiation The cluster of differentiation (also known as cluster of designation or classification determinant and of ...
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T Cell
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 ...
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Aorta-gonad-mesonephros
The aorta-gonad-mesonephros (AGM) is a region of embryonic mesoderm that develops during embryonic development from the para-aortic splanchnopleura in chick, mouse and human embryos. The very first adult definitive haematopoietic stem cells, capable of long-term multilineage repopulation of adult irradiated recipients, originate from the ventral endothelial wall of the embryonic dorsal aorta, through an endothelial transdifferentiation process referred to as an 'endothelial-to-haematopoietic transition' (EHT). In the mouse embryo, these very first HSCs are characterised by their expression of Ly6A-GFP (Sca1), CD31, CD34, cKit, CD27, CD41, Gata2, Runx1, Notch1, and BMP amongst others. The aorta-gonad-mesonephros (AGM) region is an area derived from splanchnopleura mesoderm identified in embryonic humans, mice, and non-mammalian vertebrates such as birds and zebrafish. It contains the dorsal aorta, genital ridges and mesonephros and lies between the notochord and the somatic mesod ...
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Cytokine
Cytokines are a broad and loose category of small proteins (~5–25 kDa) important in cell signaling. Cytokines are peptides and cannot cross the lipid bilayer of cells to enter the cytoplasm. Cytokines have been shown to be involved in autocrine, paracrine and endocrine signaling as immunomodulating agents. Cytokines include chemokines, interferons, interleukins, lymphokines, and tumour necrosis factors, but generally not hormones or growth factors (despite some overlap in the terminology). Cytokines are produced by a broad range of cells, including immune cells like macrophages, B lymphocytes, T lymphocytes and mast cells, as well as endothelial cells, fibroblasts, and various stromal cells; a given cytokine may be produced by more than one type of cell. They act through cell surface receptors and are especially important in the immune system; cytokines modulate the balance between humoral and cell-based immune responses, and they regulate the maturation, growth, and res ...
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CD31
Platelet endothelial cell adhesion molecule (PECAM-1) also known as cluster of differentiation 31 (CD31) is a protein that in humans is encoded by the ''PECAM1'' gene found on chromosome17q23.3. PECAM-1 plays a key role in removing aged neutrophils from the body. Structure PECAM-1 is a highly glycosylated protein with a mass of approximately 130 kDa. The structure of this protein was determined by molecular cloning in 1990, when it was found out that PECAM-1 has N-terminal domain with 574 amino acids, transmembrane domain with 19 amino acids and C-terminal cytoplasmic domain with 118 amino acids. The N-terminal domain consists of six extracellular Ig-like domains. Interactions PECAM-1 is a cell-cell adhesion protein which interacts with other PECAM-1 molecules through homophilic interactions or with non-PECAM-1 molecules through heterophilic interactions''.'' Homophilic interactions between PECAM-1 molecules are mediated by antiparallel interactions between extracellular ...
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