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HAEMATOPOIETIC GROWTH FACTORS IN ONCOLOGY
Published in James Bishop, Cancer Facts, 1999
Granulocyte-macrophage colony-stimulating factor 'GM-CSF, CSF-a, CSF-2 Sargramostim Molgramostim Regramostim Neutrophils Eosinophils Monocytes T lymphocytes, monocytes/ macrophages, fibroblasts, endothelial and epithelial cells, osteoblasts
Biotechnology products and indications I. Proteins
Published in Ronald P. Evens, Biotechnology, 2020
Growth factor (GF) proteins number 21, as listed in Table 8.4. These proteins can be divided into two areas: blood cell GFs, also known as colony-stimulating factors (CSFs), and tissue GFs, all of which are ligands to communicate between cells and stimulate new cell outcomes and functions. The CSFs are secreted by specific cells in organs, for example, erythropoietin by the kidney, and stimulate another cell type to produce an effect; in this example, bone marrow erythroid progenitors are stimulated to accelerate their production of red blood cells and correct anemia. All these GFs are produced by rDNA technology. CSF products for leukocytes are available worldwide, that is, filgrastim, pegfilgrastim, and sargramostim in the United States, and also molgramostim, regramostim, lenograstim, and nartograstim in rest of the world. Biosimilar filgrastim products include biograstim, filgrastim-Hexal, nivestim, ratiograstim, and tevagrastim. They all stimulate white blood cell production and limit infectious complications in myeloid-suppressed cancer patients. Two epoetin molecules (epoetin alfa and epoetin beta) stimulate red blood cell production, with two U.S. products available (Epogen and Procrit), along with Eprex, NeoRecormon, Silapo and Epogin in Europe and Asia. Biosimilar products for epoetin alfa are also available, such as Retacrit. Aranesp in the United States and Nespo in Europe are the hyperglycosylated products of epoetin that have extended half-lives and require less frequent dosing. A pegylated form of epoetin alfa has been developed as well to extend the dosing interval. Becaplermin is a tissue GF for the epidermis and is used to accelerate wound healing in diabetic ulcers. The second recombinant tissue GF is palifermin, impacting keratinocytes, and is used to more rapidly resolve the mucositis in cancer patients receiving chemotherapy, radiation therapy, and bone marrow transplants. Bone growth and bone fusion are accelerated with osteogenic protein-1 and platelet derived GF-BB, both GFs. Recently, neurotrophic keratitis has become treatable with a GF, oxervate. Pegylation has been used to create new GFs with longer half-lives and extended duration of action, for example, filgrastim daily is dosed daily for 5–10 d versus peg-filgrastim (Neulasta) in a single dose. Biosimilar products have also been approved for filgratim around the world; Fulphila, Nivestym, Udencya, and Zarxio.
Investigational inhaled therapies for non-CF bronchiectasis
Published in Expert Opinion on Investigational Drugs, 2018
Molgramostim (recombinant human GM-CSF) is currently used in hematological malignancies due to its potential to restore maturation of precursor cells and release into bloodstream of mature granulocytes and monocytes from bone marrow level. Molgramostim has demonstrated anti-inflammatory activities and hence is currently evaluated as an inhalatory formulation in pulmonary alveolar proteinosis, based on its modulatory effects on alveolar macrophages and on surfactant production [42].
Current management strategies and the potential of inhaled GM-CSF for the treatment of autoimmune pulmonary alveolar proteinosis
Published in Expert Opinion on Orphan Drugs, 2019
A first phase I trial was conducted in Japan on three PAP patients [47]: inhaled molgramostim was administered (125 µg twice per day every other week for 24 weeks). This report demonstrated that GM-CSF inhalation reduced foamy alveolar macrophages count in the broncho-alveolar lavage, and increased their phagocytic activity.