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ImmTAC Schematic Diagram
ImmTACs (Immune mobilising monoclonal T-cell receptors Against Cancer) are a class of bispecific biological drug being investigated for the treatment of cancer and viral infections which combines engineered cancer-recognizing TCRs with immune activating complexes. ImmTACs target cancerous or virally infected cells through binding human leukocyte antigen (HLA) presented peptide antigens and redirect the host's cytotoxic T cells to recognise and kill them. ImmTACs are fusion proteins that combine an engineered T Cell Receptor (TCR) based targeting system with a single chain antibody fragment (scFv) effector function. TCRs, like antibodies, constitute an important antigen recognition system within the immune system; but, whereas antibodies are restricted to targeting cell surface or secreted proteins TCRs can recognise peptides derived from intracellular targets presented by human leukocyte antigen (HLA). Naturally occurring TCRs are low affinity (0.18-387 micromolar range) 2-cha ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
ImmTAC Schematic Diagram
ImmTACs (Immune mobilising monoclonal T-cell receptors Against Cancer) are a class of bispecific biological drug being investigated for the treatment of cancer and viral infections which combines engineered cancer-recognizing TCRs with immune activating complexes. ImmTACs target cancerous or virally infected cells through binding human leukocyte antigen (HLA) presented peptide antigens and redirect the host's cytotoxic T cells to recognise and kill them. ImmTACs are fusion proteins that combine an engineered T Cell Receptor (TCR) based targeting system with a single chain antibody fragment (scFv) effector function. TCRs, like antibodies, constitute an important antigen recognition system within the immune system; but, whereas antibodies are restricted to targeting cell surface or secreted proteins TCRs can recognise peptides derived from intracellular targets presented by human leukocyte antigen (HLA). Naturally occurring TCRs are low affinity (0.18-387 micromolar range) 2-cha ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
CD3 (immunology)
CD3 (cluster of differentiation 3) is a protein complex and T cell co-receptor that is involved in activating both the cytotoxic T cell (CD8+ naive T cells) and T helper cells (CD4+ naive T cells). It is composed of four distinct chains. In mammals, the complex contains a CD3γ chain, a CD3δ chain, and two CD3ε chains. These chains associate with the T-cell receptor (TCR) and the CD3-zeta (ζ-chain) to generate an activation signal in T lymphocytes. The TCR, CD3-zeta, and the other CD3 molecules together constitute the TCR complex. Structure The CD3γ, CD3δ, and CD3ε chains are highly related cell-surface proteins of the immunoglobulin superfamily containing a single extracellular immunoglobulin domain. A structure of the extracellular and transmembrane regions of the CD3γε/CD3δε/CD3ζζ/TCRαβ complex was solved with CryoEM, showing for the first time how the CD3 transmembrane regions enclose the TCR transmembrane regions in an open barrel. Containing aspartate ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Apoptosis
Apoptosis (from grc, ἀπόπτωσις, apóptōsis, 'falling off') is a form of programmed cell death that occurs in multicellular organisms. Biochemical events lead to characteristic cell changes (morphology) and death. These changes include blebbing, cell shrinkage, nuclear fragmentation, chromatin condensation, DNA fragmentation, and mRNA decay. The average adult human loses between 50 and 70 billion cells each day due to apoptosis. For an average human child between eight and fourteen years old, approximately twenty to thirty billion cells die per day. In contrast to necrosis, which is a form of traumatic cell death that results from acute cellular injury, apoptosis is a highly regulated and controlled process that confers advantages during an organism's life cycle. For example, the separation of fingers and toes in a developing human embryo occurs because cells between the digits undergo apoptosis. Unlike necrosis, apoptosis produces cell fragments called apoptotic ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Granzyme
Granzymes are serine proteases released by cytoplasmic granules within cytotoxic T cells and natural killer (NK) cells. They induce programmed cell death (apoptosis) in the target cell, thus eliminating cells that have become cancerous or are infected with viruses or bacteria. Granzymes also kill bacteria and inhibit viral replication. In NK cells and T cells, granzymes are packaged in cytotoxic granules along with perforin. Granzymes can also be detected in the rough endoplasmic reticulum, golgi complex, and the trans-golgi reticulum. The contents of the cytotoxic granules function to permit entry of the granzymes into the target cell cytosol. The granules are released into an immune synapse formed with a target cell, where perforin mediates the delivery of the granzymes into endosomes in the target cell, and finally into the target cell cytosol. Granzymes are part of the serine esterase family. They are closely related to other immune serine proteases expressed by innate immune cel ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Perforin
Perforin-1 is a protein that in humans is encoded by the ''PRF1'' gene and the ''Prf1'' gene in mice. Function Perforin is a pore forming cytolytic protein found in the granules of cytotoxic T lymphocytes (CTLs) and natural killer cells (NK cells). Upon degranulation, perforin molecules translocate to the target cell with the help of calreticulin, which works as a chaperone protein to prevent perforin from degrading. Perforin then binds to the target cell's plasma membrane via membrane phospholipids while phosphatidylcholine binds calcium ions to increase perforin's affinity to the membrane. Perforin oligomerises in a Ca2+ dependent manner to form pores on the target cell. The pore formed allows for the passive diffusion of a family of pro-apoptotic proteases, known as the granzymes, into the target cell. The lytic membrane-inserting part of perforin is the MACPF domain. This region shares homology with cholesterol-dependent cytolysins from Gram-positive bacteria. Perforin has ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Co-stimulatory
Co-stimulation is a secondary signal which immune cells rely on to activate an immune response in the presence of an antigen-presenting cell. In the case of T cells, two stimuli are required to fully activate their immune response. During the activation of lymphocytes, co-stimulation is often crucial to the development of an effective immune response. Co-stimulation is required in addition to the antigen-specific signal from their antigen receptors. T cell co-stimulation T cells require two signals to become fully activated. A first signal, which is antigen-specific, is provided through the T cell receptor (TCR) which interacts with peptide- MHC molecules on the membrane of antigen presenting cells (APC). A second signal, the co-stimulatory signal, is antigen nonspecific and is provided by the interaction between co-stimulatory molecules expressed on the membrane of APC and the T cell. One of the best characterized co-stimulatory molecules expressed by T cells is CD28, which inter ... [...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] |
Co-receptor
A co-receptor is a cell surface receptor that binds a signalling molecule in addition to a primary receptor in order to facilitate ligand recognition and initiate biological processes, such as entry of a pathogen into a host cell. Properties The term co-receptor is prominent in literature regarding signal transduction, the process by which external stimuli regulate internal cellular functioning.Gomperts, BD.; Kramer, IM. Tatham, PER. (2002). Signal transduction. Academic Press. ISBN. The key to optimal cellular functioning is maintained by possessing specific machinery that can carry out tasks efficiently and effectively. Specifically, the process through which intermolecular reactions forward and amplify extracellular signals across the cell surface has developed to occur by two mechanisms. First, cell surface receptors can directly transduce signals by possessing both serine and threonine or simply serine in the cytoplasmic domain. They can also transmit signals through adaptor m ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Bi-specific T-cell Engager
Bi-specific T-cell engagers (BiTEs) are a class of artificial bispecific monoclonal antibodies that are investigated for use as anti-cancer drugs. They direct a host's immune system, more specifically the T cells' cytotoxic activity, against cancer cells. ''BiTE'' is a registered trademark of Micromet AG (fully owned subsidiary of Amgen Inc). BiTEs are fusion proteins consisting of two single-chain variable fragments (scFvs) of different antibodies, or amino acid sequences from four different genes, on a single peptide chain of about 55 kilodaltons. One of the scFvs binds to T cells via the CD3 receptor, and the other to a tumor cell via a tumor specific molecule. Mechanism of action Like other bispecific antibodies, and unlike ordinary monoclonal antibodies, BiTEs form a link between T cells and tumor cells. This causes T cells to exert cytotoxic activity on tumor cells by producing proteins like perforin and granzymes, independently of the presence of MHC I or co-stimulatory ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Wiki ImmTAC Mechanism Of Action Diseased Cell
A wiki ( ) is an online hypertext publication Collaborative editing, collaboratively edited and managed by its own audience, using a web browser. A typical wiki contains multiple pages for the subjects or scope of the project, and could be either open to the public or limited to use within an organization for maintaining its internal knowledge base. Wikis are enabled by wiki software, otherwise known as wiki engines. A wiki engine, being a form of a content management system, differs from other web application, web-based systems such as blog software, in that the content is created without any defined owner or leader, and wikis have little inherent structure, allowing structure to emerge according to the needs of the users. Wiki engines usually allow content to be written using a simplified markup language and sometimes edited with the help of a Online rich-text editor, rich-text editor. There are dozens of different wiki engines in use, both standalone and part of other sof ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Phage Display
Phage display is a laboratory technique for the study of protein–protein, protein–peptide, and protein– DNA interactions that uses bacteriophages (viruses that infect bacteria) to connect proteins with the genetic information that encodes them. In this technique, a gene encoding a protein of interest is inserted into a phage coat protein gene, causing the phage to "display" the protein on its outside while containing the gene for the protein on its inside, resulting in a connection between genotype and phenotype. These displaying phages can then be screened against other proteins, peptides or DNA sequences, in order to detect interaction between the displayed protein and those other molecules. In this way, large libraries of proteins can be screened and amplified in a process called ''in vitro'' selection, which is analogous to natural selection. The most common bacteriophages used in phage display are M13 and fd filamentous phage, though T4, T7, and λ phage have ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Fusion Protein
Fusion proteins or chimeric (kī-ˈmir-ik) proteins (literally, made of parts from different sources) are proteins created through the joining of two or more genes that originally coded for separate proteins. Translation of this ''fusion gene'' results in a single or multiple polypeptides with functional properties derived from each of the original proteins. ''Recombinant fusion proteins'' are created artificially by recombinant DNA technology for use in biological research or therapeutics. '' Chimeric'' or ''chimera'' usually designate hybrid proteins made of polypeptides having different functions or physico-chemical patterns. ''Chimeric mutant proteins'' occur naturally when a complex mutation, such as a chromosomal translocation, tandem duplication, or retrotransposition creates a novel coding sequence containing parts of the coding sequences from two different genes. Naturally occurring fusion proteins are commonly found in cancer cells, where they may function as oncoproteins ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
