APG101
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APG101
Asunercept ( INN; development codes APG101 and CAN008) is a soluble CD95-Fc fusion protein which is in clinical development for the treatment of glioblastoma multiforme (GBM) and myelodysplastic syndromes (MDS). Asunercept has been granted orphan drug status for the treatment of GBM and MDS in the EU and the US. It has also received PRIME designation by the European Medicines Agency (EMA) for the treatment of GBM. __TOC__ Mechanism of action Asunercept blocks the CD95–ligand ( CD95L) from binding to the CD95-receptor (CD95), which induces apoptosis. In oncology, this blockade is intended to prevent the killing of activated T cells that can be induced by tumor-associated macrophages (TAMs), endothelial cells, or fibroblasts. In MDS, CD95L-signaling is a negative regulator of erythrocyte production in the bone marrow and its blockade has been shown to rescue erythroid progenitors. Clinical development A randomized, double-blind, placebo-controlled phase I study to examine ...
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CD95L
Fas ligand (FasL or CD95L or CD178) is a type-II transmembrane protein that belongs to the tumor necrosis factor (TNF) family. Its binding with its receptor induces apoptosis. Fas ligand/receptor interactions play an important role in the regulation of the immune system and the progression of cancer. Structure Fas ligand or FasL is a homotrimeric type II transmembrane protein expressed on cytotoxic T lymphocytes. It signals through trimerization of FasR, which spans the membrane of the "target" cell. This trimerization usually leads to apoptosis, or cell death. Soluble Fas ligand is generated by cleaving membrane-bound FasL at a conserved cleavage site by the external matrix metalloproteinase MMP-7. Receptors *FasR: The Fas receptor ( FasR), or CD95, is the most intensely studied member of the death receptor family. The gene is situated on chromosome 10 in humans and 19 in mice. Previous reports have identified as many as eight splice variants, which are translated into s ...
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Endothelial Cells
The endothelium is a single layer of squamous endothelial cells that line the interior surface of blood vessels and lymphatic vessels. The endothelium forms an interface between circulating blood or lymph in the lumen and the rest of the vessel wall. Endothelial cells form the barrier between vessels and tissue and control the flow of substances and fluid into and out of a tissue. Endothelial cells in direct contact with blood are called vascular endothelial cells whereas those in direct contact with lymph are known as lymphatic endothelial cells. Vascular endothelial cells line the entire circulatory system, from the heart to the smallest capillaries. These cells have unique functions that include fluid filtration, such as in the glomerulus of the kidney, blood vessel tone, hemostasis, neutrophil recruitment, and hormone trafficking. Endothelium of the interior surfaces of the heart chambers is called endocardium. An impaired function can lead to serious health issues ...
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Antineoplastic Drugs
Chemotherapy (often abbreviated to chemo and sometimes CTX or CTx) is a type of cancer treatment that uses one or more anti-cancer drugs (chemotherapeutic agents or alkylating agents) as part of a standardized chemotherapy regimen. Chemotherapy may be given with a curative intent (which almost always involves combinations of drugs) or it may aim to prolong life or to reduce symptoms (palliative chemotherapy). Chemotherapy is one of the major categories of the medical discipline specifically devoted to pharmacotherapy for cancer, which is called ''medical oncology''. The term ''chemotherapy'' has come to connote non-specific usage of intracellular poisons to inhibit mitosis (cell division) or induce DNA damage, which is why inhibition of DNA repair can augment chemotherapy. The connotation of the word chemotherapy excludes more selective agents that block extracellular signals (signal transduction). The development of therapies with specific molecular or genetic targets, w ...
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Cytopenias
Cytopenia is a reduction in the number of mature blood cells. It is common in cancer patients being treated with radiation and/or chemotherapy. Types Anemia – a reduction of the red blood cells in the body. Leukopenia – a deficiency of white blood cells, or leukocytes Neutropenia – a type of leukopenia, with a specific deficiency in neutrophils Thrombocytopenia – a deficiency of platelets Pancytopenia – when all three types of blood cells; red blood cells, white blood cells, and platelets, are all deficient. This is a life-threatening disorder that is a characteristic of aplastic anemia. There are also two general types of cytopenia: autoimmune and refractory. Autoimmune cytopenia – caused by an autoimmune disease when your body produces antibodies to destroy the healthy blood cells. Refractory cytopenia – caused by bone marrow not producing healthy blood cells, and can be a result of cancer. Symptoms and signs The symptoms of cytopenia vary depending on w ...
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Progression-free Survival
Progression-free survival (PFS) is "the length of time during and after the treatment of a disease, such as cancer, that a patient lives with the disease but it does not get worse". In oncology, PFS usually refers to situations in which a tumor is present, as demonstrated by laboratory testing, radiologic testing, or clinically. Similarly, "disease-free survival" is the length of time after patients have received treatment and have no detectable disease. Time to progression (TTP) does not count patients who die from other causes but is otherwise a close equivalent to PFS (unless there are many such events). The FDA gives separate definitions and prefers PFS. Background PFS is widely used as a surrogate endpoint in oncology. The definition of "progression" generally involves imaging techniques (plain radiograms, CT scans, MRI, PET scans, ultrasounds) or other aspects: biochemical progression may be defined on the basis of an increase in a tumor marker (such as CA125 for epithelia ...
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Randomized Controlled Trial
A randomized controlled trial (or randomized control trial; RCT) is a form of scientific experiment used to control factors not under direct experimental control. Examples of RCTs are clinical trials that compare the effects of drugs, surgical techniques, medical devices, diagnostic procedures or other medical treatments. Participants who enroll in RCTs differ from one another in known and unknown ways that can influence study outcomes, and yet cannot be directly controlled. By randomly allocating participants among compared treatments, an RCT enables ''statistical control'' over these influences. Provided it is designed well, conducted properly, and enrolls enough participants, an RCT may achieve sufficient control over these confounding factors to deliver a useful comparison of the treatments studied. Definition and examples An RCT in clinical research typically compares a proposed new treatment against an existing standard of care; these are then termed the 'experime ...
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Erythrocyte
Red blood cells (RBCs), also referred to as red cells, red blood corpuscles (in humans or other animals not having nucleus in red blood cells), haematids, erythroid cells or erythrocytes (from Greek ''erythros'' for "red" and ''kytos'' for "hollow vessel", with ''-cyte'' translated as "cell" in modern usage), are the most common type of blood cell and the vertebrate's principal means of delivering oxygen (O2) to the body tissues—via blood flow through the circulatory system. RBCs take up oxygen in the lungs, or in fish the gills, and release it into tissues while squeezing through the body's capillaries. The cytoplasm of a red blood cell is rich in hemoglobin, an iron-containing biomolecule that can bind oxygen and is responsible for the red color of the cells and the blood. Each human red blood cell contains approximately 270 million hemoglobin molecules. The cell membrane is composed of proteins and lipids, and this structure provides properties essential for physio ...
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Fibroblasts
A fibroblast is a type of biological cell that synthesizes the extracellular matrix and collagen, produces the structural framework ( stroma) for animal tissues, and plays a critical role in wound healing. Fibroblasts are the most common cells of connective tissue in animals. Structure Fibroblasts have a branched cytoplasm surrounding an elliptical, speckled nucleus having two or more nucleoli. Active fibroblasts can be recognized by their abundant rough endoplasmic reticulum. Inactive fibroblasts (called fibrocytes) are smaller, spindle-shaped, and have a reduced amount of rough endoplasmic reticulum. Although disjointed and scattered when they have to cover a large space, fibroblasts, when crowded, often locally align in parallel clusters. Unlike the epithelial cells lining the body structures, fibroblasts do not form flat monolayers and are not restricted by a polarizing attachment to a basal lamina on one side, although they may contribute to basal lamina component ...
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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 ...
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Macrophages
Macrophages (abbreviated as M φ, MΦ or MP) ( el, large eaters, from Greek ''μακρός'' (') = large, ''φαγεῖν'' (') = to eat) are a type of white blood cell of the immune system that engulfs and digests pathogens, such as cancer cells, microbes, cellular debris, and foreign substances, which do not have proteins that are specific to healthy body cells on their surface. The process is called phagocytosis, which acts to defend the host against infection and injury. These large phagocytes are found in essentially all tissues, where they patrol for potential pathogens by amoeboid movement. They take various forms (with various names) throughout the body (e.g., histiocytes, Kupffer cells, alveolar macrophages, microglia, and others), but all are part of the mononuclear phagocyte system. Besides phagocytosis, they play a critical role in nonspecific defense ( innate immunity) and also help initiate specific defense mechanisms ( adaptive immunity) by recruiting oth ...
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Glioblastoma Multiforme
Glioblastoma, previously known as glioblastoma multiforme (GBM), is one of the most aggressive types of cancer that begin within the brain. Initially, signs and symptoms of glioblastoma are nonspecific. They may include headaches, personality changes, nausea, and symptoms similar to those of a stroke. Symptoms often worsen rapidly and may progress to unconsciousness. The cause of most cases of glioblastoma is not known. Uncommon risk factors include genetic disorders, such as neurofibromatosis and Li–Fraumeni syndrome, and previous radiation therapy. Glioblastomas represent 15% of all brain tumors. They can either start from normal brain cells or develop from an existing low-grade astrocytoma. The diagnosis typically is made by a combination of a CT scan, MRI scan, and tissue biopsy. There is no known method of preventing the cancer. Treatment usually involves surgery, after which chemotherapy and radiation therapy are used. The medication temozolomide is frequently use ...
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