Clinical use of hemocytokines

Cancer is a disease that affects the immune system. Its spreadability through the body is a risk to life. Preventing such a spread is the most burning issue for the entire scientific world. Dozens of clinical studies and developed drugs are aimed at strengthening the immune system, reducing the tumour and preventing its spread. The news that I want to share with you in this report is one of the positive achievements of recent times, giving hope for life to skin cancer patients.

The results of clinical trials have shown that the combination of Yervoy® (sygramumab: GM-CSF) instead of using only Yervoy® in the treatment of advanced melanoma (metastatic), which is an aggressive type of skin cancer, can prolong the life of the patient. The positive results were announced at the meeting in 2013 of the American Society of Clinical Oncology.

Every year around the world, more than a million people are diagnosed with skin cancer, with about 68,000 diagnoses associated with melanoma. Melanoma is more dangerous than other types of skin cancer, as it increases the risk of death due to greater spread.

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Immunotherapy is a form of treatment aimed at activating the immune system to attack cancer cells and preventing the spread of the disease. The drug “Yervoy”, which is used for the immune system in immunotherapy, is a drug with the purpose of the CTLA4 molecule, which is on the surface of the T cell, which is a protective cell of the body in the treatment of melanoma at an advanced stage, and prevents the immune reaction. Leukine is a growth factor that is used to increase the number of white blood cells after stem cell transplantation or after chemotherapy.

The researchers began evaluating the combination of Yervoy-Leukine in treatment, combining these two reactions. In clinical trials of 245 patients with advanced melanoma, only Yervoy was given to the patients who received the medication; the other part was given the combination of Yervoy-Leukine.

Wide clinical use of hemocytokines became possible after their preparation in recombinant form. The method of obtaining a recombinant protein involves the introduction of a gene encoding it into the genome of cells grown in culture. These cells (bacterial, fungal or mammalian cells) begin to synthesize the product of the inserted gene (e.g., a cytokine) and thus this cytokine can be obtained in significant amounts. The first hemocytokines obtained in a recombinant form in the early 1980s were granulocyte-macrophage (GM-CSF) and granulocyte (G-CSF) colony-stimulating factors.

Another direction is the use of erythropoietin to correct anaemia in patients with kidney damage on hemodialysis. Also, G-CSF and GM-CSF can be used to stimulate the anti-infective properties of phagocytes in patients with severe infection. Variants of the use of hemocytokines in immunology as vaccine adjuvants and genotrace for the isolation of long-lived stem cells are discussed. At present, oncology remains the main area of application of these drugs.

The extent and duration of nyphopenia, which develops after chemotherapeutic treatment, largely depends on the number of infectious complications and lethality.

Typically, these drugs are used to prevent or reduce the duration and severity of post-cytostatic neutropenia and reduce the risk of infection. There are other ways of using myeloid growth factors.

The clinic currently uses four myelocytokines. Two of them are human recombinant granulocyte growth factors – filgrastim and lenograstim and two others refer to human recombinant granulocyte-macrophage growth factors -molgabilities and sargrasmicity.

Also, filgrastim has one amino acid in its composition more than lenograstim. According to some authors, carbohydrate residues can protect the molecule from conformational changes and proteolysis and enhance the biological effect in vitro. However, according to some data, the clearance of the glycosylated cytokine is higher, and at an equal dose a greater concentration of non-glycosylated protein in plasma is achieved.

Molgramostim(GM-CSF) is also synthesized by the E. coli and, in contrast to sargrasmostoma, produced by cells of yeast fungi, has a non-glycosylated molecule. Non-glycosylated forms of GM-CSF have greater proliferation-stimulating activity, which some authors explain by facilitating binding to the receptor. Endothelial cells and fibroblasts, which are an important source of GM-CSF in the body, can synthesize and secrete it in a non-glycosylated form.

Three myelocytokines were registered for clinical use: neugogen (filgrastim) -neglycosylated recombinant human G-CSF, granotite (lenograstim) -glycosylated recombinant human G-CSF, leukomax (molgamostim) -neglycosylated recombinant human GM-CSF.

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