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PD-1 And PD-L1 Inhibitors
PD-1 inhibitors and PD-L1 inhibitors are a group of checkpoint inhibitor anticancer drugs that block the activity of PD-1 and PDL1 immune checkpoint proteins present on the surface of cells. Immune checkpoint inhibitors are emerging as a front-line treatment for several types of cancer. PD-1 and PD-L1 inhibitors act to inhibit the association of the programmed death-ligand 1 (PD-L1) with its receptor, programmed cell death protein 1 (PD-1). The interaction of these cell surface proteins is involved in the suppression of the immune system and occurs following infection to limit the killing of bystander host cells and prevent autoimmune disease. This immune checkpoint is also active in pregnancy, following tissue allografts, and in different types of cancer. History The concept of blocking PD-1 and PD-L1 for the treatment of cancer was first published in 2001. Pharmaceutical companies began attempting to develop drugs to block these molecules, and the first clinical trial was lau ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
PD-L1 Positive Lung Adenocarcinoma -- High Mag
Programmed death-ligand 1 (PD-L1) also known as cluster of differentiation 274 (CD274) or B7 homolog 1 (B7-H1) is a protein that in humans is encoded by the ''CD274'' gene. Programmed death-ligand 1 (PD-L1) is a 40kDa type 1 transmembrane protein that has been speculated to play a major role in suppressing the adaptive arm of immune systems during particular events such as pregnancy, tissue allografts, autoimmune disease and other disease states such as hepatitis. Normally the adaptive immune system reacts to antigens that are associated with immune system activation by exogenous or endogenous danger signals. In turn, clonal expansion of antigen-specific CD8+ T cells and/or CD4+ helper cells is propagated. The binding of PD-L1 to the inhibitory checkpoint molecule PD-1 transmits an inhibitory signal based on interaction with phosphatases (SHP-1 or SHP-2) via Immunoreceptor Tyrosine-Based Switch Motif (ITSM). This reduces the proliferation of antigen-specific T-cells in lymph nod ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Tumor
A neoplasm () is a type of abnormal and excessive growth of tissue. The process that occurs to form or produce a neoplasm is called neoplasia. The growth of a neoplasm is uncoordinated with that of the normal surrounding tissue, and persists in growing abnormally, even if the original trigger is removed. This abnormal growth usually forms a mass, when it may be called a tumor. ICD-10 classifies neoplasms into four main groups: benign neoplasms, in situ neoplasms, malignant neoplasms, and neoplasms of uncertain or unknown behavior. Malignant neoplasms are also simply known as cancers and are the focus of oncology. Prior to the abnormal growth of tissue, as neoplasia, cells often undergo an abnormal pattern of growth, such as metaplasia or dysplasia. However, metaplasia or dysplasia does not always progress to neoplasia and can occur in other conditions as well. The word is from Ancient Greek 'new' and 'formation, creation'. Types A neoplasm can be benign, potentially m ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Merck Serono
Merck Serono (EMD Serono in the United States and Canada) is a pharmaceutical company headquartered in Darmstadt, Germany, and a brand and division of Merck focused on biopharmaceuticals. In September 2006, Merck KGaA announced its intent to purchase the majority of Serono shares from Ernesto Bertarelli and the Bertarelli family. The Merck-Serono merger was announced on 21 September 2006. Merck KGaA and Serono operated as distinct entities until at least January 2007. As of January 5, 2007, Merck held the majority shares of Serono. The new company is called Merck Serono international SA. In 2012, Merck Serono moved its headquarters from Geneva, Switzerland to Darmstadt. Drugs they market include Erbitux, UFT, Rebif, Mavenclad, Novantrone, Gonal, Ovidrel/ Ovitrelle, Zorbtive, Luveris, Saizen, Serostim, Glucophage, Concor and Euthyrox. Raptiva was withdrawn in 2007. In the U.S. and Canada, Merck Serono is known as EMD Serono, as the former Merck subsidiary Merck & Co. h ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
ICOS (gene)
Inducible T-cell costimulator is an immune checkpoint protein that in humans is encoded by the ''ICOS'' gene. CD278 or ICOS (Inducible T-cell COStimulator) is a CD28-superfamily costimulatory molecule that is expressed on activated T cells. It is thought to be important for Th2 cells in particular. Function The protein encoded by this gene belongs to the CD28 and CTLA-4 cell-surface receptor family. It forms homodimers and plays an important role in cell-cell signaling, immune responses and regulation of cell proliferation. Knockout phenotype Compared to wild-type naïve T cells, ICOS-/- T cells activated with plate-bound anti- CD3 have reduced proliferation and IL-2 secretion. The defect in proliferation can be rescued by addition of IL-2 to the culture, suggesting the proliferative defect is due either to ICOS-mediated IL-2 secretion or the activation of similar signaling pathways between ICOS and IL-2. In terms of Th1 and Th2 cytokine secretion, ICOS-/- CD4+ T cell ac ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
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 ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Poly ADP Ribose Polymerase
Poly (ADP-ribose) polymerase (PARP) is a family of proteins involved in a number of cellular processes such as DNA repair, genomic stability, and programmed cell death. Members of PARP family The PARP family comprises 17 members (10 putative). They vary greatly in structure and function within the cell. * ''PARP1'', '' PARP2'', VPARP (''PARP4''), Tankyrase-1 and -2 (PARP-5a or ''TNKS'', and PARP-5b or ''TNKS2'') have a confirmed PARP activity. * Others include ''PARP3'', , ''TIPARP'' (or "PARP7"), ''PARP8'', , ''PARP10'', , ''PARP12'', , , and ''PARP16 (gene), PARP16''. Structure PARP is composed of four domains of interest: a DNA-binding domain, a caspase-cleaved domain (see below), an auto-modification domain, and a catalytic domain. The DNA-binding domain is composed of two zinc finger structural motif, motifs. In the presence of damaged DNA (base pair-excised), the DNA-binding domain will bind the DNA and induce a Allosteric regulation, conformational shift. It has been ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
OX40
Tumor necrosis factor receptor superfamily, member 4 (TNFRSF4), also known as CD134 and OX40 receptor, is a member of the TNFR-superfamily of receptors which is not constitutively expressed on resting naïve T cells, unlike CD28. OX40 is a secondary co-stimulatory immune checkpoint molecule, expressed after 24 to 72 hours following activation; its ligand, OX40L, is also not expressed on resting antigen presenting cells, but is following their activation. Expression of OX40 is dependent on full activation of the T cell; without CD28, expression of OX40 is delayed and of fourfold lower levels. Function OX40 has no effect on the proliferative abilities of CD4+ cells for the first three days, however after this time proliferation begins to slow and cells die at a greater rate, due to an inability to maintain a high level of PKB activity and expression of Bcl-2, Bcl-XL and survivin. OX40L binds to OX40 receptors on T-cells, preventing them from dying and subsequently increasing cytoki ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Killer-cell Immunoglobulin-like Receptor
Killer-cell immunoglobulin-like receptors (KIRs), are a family of type I transmembrane glycoproteins expressed on the plasma membrane of natural killer (NK) cells and a minority of T cells. At least 15 genes and 2 pseudogenes encoding KIR map in a 150-kb region of the leukocyte receptor complex (LRC) on human chromosome 19q13.4. They regulate the killing function of these cells by interacting with major histocompatibility (MHC) class I molecules, which are expressed on all nucleated cell types. KIR receptors can distinguish between MHC I allelic variants, which allows them to detect virally infected cells or transformed cells. KIRs are paired receptors with both activating and inhibitory functions; most KIRs are inhibitory: their recognition of MHC molecules suppresses the cytotoxic activity of their NK cell. A limited number of KIRs are activating: their recognition of MHC molecules activates the cytotoxic activity of their cell. Initial expression of KIRs on NK cel ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
B7-H3
Cluster of Differentiation 276 (CD276) or B7 Homolog 3 (B7-H3) is a human protein encoded by the gene. Structure B7-H3 is a 316 amino acid-long type I transmembrane protein, existing in two isoforms determined by its extracellular domain. In mice, the extracellular domain consists of a single pair of immunoglobulin variable (IgV)-like and immunoglobulin constant (IgC)-like domains, whereas in humans it consists of one pair (2Ig-B7-H3) or two identical pairs (4Ig-B7-H3) due to exon duplication. B7-H3 mRNA is expressed in most normal tissues. In contrast, B7-H3 protein has a very limited expression on normal tissues because of its post-transcriptional regulation by microRNAs. However, B7-H3 protein is expressed at high frequency on many different cancer types (60% of all cancers). Function In non-malignant tissues, B7-H3 has a predominantly inhibitory role in adaptive immunity, suppressing T cell activation and proliferation. In malignant tissues, B7-H3 is an immune check ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
LAG3
Lymphocyte-activation gene 3, also known as LAG-3, is a protein which in humans is encoded by the ''LAG3'' gene. LAG3, which was discovered in 1990 and was designated CD223 (cluster of differentiation 223) after the Seventh Human Leucocyte Differentiation Antigen Workshop in 2000, is a cell surface molecule with diverse biologic effects on T cell function. It is an immune checkpoint receptor and as such is the target of various drug development programs by pharmaceutical companies seeking to develop new treatments for cancer and autoimmune disorders. In soluble form it is also being developed as a cancer drug in its own right. Gene The LAG3 gene contains 8 exons. The sequence data, exon/ intron organization, and chromosomal localization all indicate a close relationship of LAG3 to CD4. The gene for LAG-3 lies adjacent to the gene for CD4 on human chromosome 12 (12p13) and is approximately 20% identical to the CD4 gene. Protein The LAG3 protein, which belongs to immunoglob ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Ipilimumab
Ipilimumab, sold under the brand name Yervoy, is a monoclonal antibody medication that works to activate the immune system by targeting CTLA-4, a protein receptor that downregulates the immune system. Cytotoxic T lymphocytes (CTLs) can recognize and destroy cancer cells. However, an inhibitory mechanism interrupts this destruction. Ipilimumab turns off this inhibitory mechanism and boosts the body's immune response against cancer cells. Ipilimumab was approved by the US Food and Drug Administration (FDA) in March 2011, for the treatment of melanoma, a type of skin cancer. It is undergoing clinical trials for the treatment of non-small cell lung carcinoma (NSCLC), small cell lung cancer (SCLC), (completed) bladder cancer (completed) and metastatic hormone-refractory prostate cancer. The concept of using anti-CTLA4 antibodies to treat cancer was first developed by James P. Allison while he was director of the Cancer Research Laboratory at the University of California, Berkeley. Cl ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
CTLA4
CTLA-4 or CTLA4 (cytotoxic T-lymphocyte-associated protein 4), also known as CD152 (cluster of differentiation 152), is a protein receptor that functions as an immune checkpoint and downregulates immune responses. CTLA-4 is constitutively expressed in regulatory T cells but only upregulated in conventional T cells after activation – a phenomenon which is particularly notable in cancers. It acts as an "off" switch when bound to CD80 or CD86 on the surface of antigen-presenting cells. The CTLA-4 protein is encoded by the ''Ctla-4'' gene in mice and the ''CTLA-4'' gene in humans. History CTLA-4 was first identified in 1991 as a second receptor for the T cell costimulation ligand B7. In November 1995, the labs of Tak Wah Mak and Arlene H. Sharpe independently published their findings on the discovery of the function of CTLA-4 as a negative regulator of T-cell activation, by knocking out the gene in mice. Previous studies from several labs had used methods which could not defi ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
