Immunotherapeutics

use immunotherapeutics or modify defense mechanisms. The use of these agents is progressing rapidly. Certainly, new classes, new agents and other applications for existing drugs to be developed. A number of different classes of immune therapeutics have been developed (see table: Some immunotherapeutics in clinical use *): Monoclonal antibody fusion proteins soluble cytokine receptors Recombinant cytokines, small molecule mimics of cell therapies Some immunotherapeutics in clinical use * drug effects indications Monoclonal Antibody Adalimumab Anti-TNF ? Moderate to severe pronounced rheumatoid arthritis (RA) plaque psoriasis Moderate to severe Crohn’s disease refractory to standard treatments ulcerative colitis ankylosing spondylitis psoriatic arthritis Moderate to severe polyarticular juvenile idiopathic arthritis alemtuzumab anti-B-cell (CD52) Chronic lymphocytic B-cell leukemia refractory to standard treatments basiliximab anti-IL-2 receptor prevention of acute kidney rejection belimumab anti-lymphocyte n-stimulator B protein (anti-BLyS) autoantibody-positive SLE in adults who receive a standard treatment Brentuximab vedotin anti-CD30 (associated with the antimitotic monomethyl auristatin E) Hodgkin’s lymphoma after failure of autologous stem cell transplantation (ASCT) or at least 2 cycles of chemotherapy with a plurality of drugs in patients who have not received autologous stem cell systemic anaplastic large cell lymphoma after failure of at least one chemotherapy with multiple medications canakinumab anti-IL-1? cryopyrin-associated periodic syndromes (Cryopyrino pathies) in patients ? 4 years Juvenile Idiopathic Arthritis in patients ? 2 years certolizumab (pegylated Fab fragment) anti-TNF-? Moderate to severe rheumatoid arthritis in adults moderate to severe Crohn’s disease, when conventional treatments were not sufficient psoriatic arthritis ankylosing spondylitis daclizumab anti-IL-2 receptor prevention of acute kidney rejection eculizumab anti-complement component C5 paroxysmal nocturnal Hämog lobinurie atypical hemolytic uremic syndrome golimumab anti-TNF-? agent severity are intolerant to severe rheumatoid arthritis (in combination with methotrexate) psoriatic arthritis ankylosing spondylitis Moderate to severe ulcerative colitis, if patients respond adequately to the primary treatment or towards it or when an ongoing corticosteroids need ibritumomab anti-B cell (CD20, bound to the radioactive drug yttrium 90) relapsed or refractory low-gradige follicular or transformed non-Hodgkin’s B-cell lymphomas Infliximab anti-TNF-? Moderate to severe Crohn’s disease or ulcerative colitis, when an inadequate response to conventional treatments Moderate to severe rheumatoid arthritis severity (in combination with methotrexate) Active ankylosing spondylitis active psoriatic arthritis chronic plaque psoriasis when other treatments are less suitable ipilimumab anti-CTLA-4 inoperable or metastatic, advanced melanoma natalizumab anti-?4-integrin subunit Relapsing-remitting multiple sclerosis or Crohn’s disease when ande re treatments are insufficient ofatumumab anti-B-cell (CD20) CLL refractory to fludarabine and alemtuzumab Omalizumab Anti-IgE Medium weight to severe asthma in patients> 12 years with documented allergic diseases that are not adequately controlled on inhaled corticosteroids Chronic idiopathic urticaria in patients ? 12 years who remain symptomatic despite H1 antihistamine treatment refractory rituximab anti-B cell (CD20) Relapsed or res CD20 +, low-gradiges or follicular non-Hodgkin’s B-cell lymphoma CD20 + CLL (used in combination with fludarabine and cyclophosphamide) Moderate to severe rheumatoid arthritis (in combination with methotrexate) with an inadequate response to TNF antagonists granulomatosis with polyangiitis (Wegener’s granulomatosis) Microscopic polyangiitis siltuximab anti-IL-6 Multicentric Castleman’s disease in patients who are HIV and HHV-8-negative tocilizumab anti-IL-6 receptor (anti-IL-6R) Moderate to severe rheumatoid arthritis in inadequate response to TNF antagonists Polyarticular or systemic juvenile idiopathic e arthritis in patients ? 2 years Tositumomab anti-B cell (CD20, which are bound to radioactive iodine [131I]) Refractory and recurrent CD20 + low-gradiges follicular or transformed non-Hodgkin’s lymphoma ustekinumab anti-IL-12 and IL-23 moderate to severe plaque psoriasis psoriatic arthritis Vedolizumab anti-?4?7 integrin moderate to severe active ulcerative colitis when inadequate response to conventional therapy or TNF antagonists moderate to severe Crohn Disease when conventional therapy or TNF antagonist fusion proteins were not sufficient Abatacept (CTLA-4 extracellular domain of the Fc region of IgG1) inhibition of T cell activation Moderate to severe marked rheumatoid arthritis Denileukin diftitox (fusion of IL-2 to diphtheria toxin) transfer of the toxin to CD25 component of the IL-2 receptor CD25 + cutaneous T-cell lymphoma etanercept (fusion of TNF-? 2 CD120b receptors on Fc region of IgG1) Decrease in TNF levels Rheumatoid arthritis Polyarticular juvenile idiopathic arthritis in patients ? 2 years psoriatic arthritis ankylosing spondylitis plaque psoriasis soluble cytokine receptors anakinra (IL-1 receptor antagonist, sometimes pegylated for long half-life) Competitive inhibition of IL-1? and IL -1? activities in patients ? 18 years: Moderate to severe RA, cryopyrin-associated periodic syndromes cytokines IFN-? Antiproliferative and antiviral In patients ? 18 years: Chronic hepatitis C, AIDS-related Kaposi’s sarcoma, hairy cell leukemia, chronic myelogenous leukemia, metastatic melanoma IFN-? antiproliferative and antiviral reduction in the number of relapses in relapsing-remitting multiple sclerosis IFN-? immune stimulatory and anti-viral control infection, chronic granulomatous disease, delay of progression in severe, malignant osteopetrosis IL-2 immunostimulatory Metastatic renal cell carcinoma and metastatic melanoma IL-11 Thrombopoietischer growth factor prevention of thrombocytopenia following myelosuppressive chemotherapy G-CSF stimulation of granulocyte production reversal of neutropenia after chemotherapy, radiation therapy, or both GM-CSF stimulation of granulocyte and monocyte / macrophage production reversal of neutropenia after chemotherapy, radiation therapy, or both Cell therapy Sipuleucel T Autologous circulating ICAM-1 + peripheral blood mononuclear cells activated with prostate-specific acid phosphatase and GM-CSF Asymptomatic or minimally symptomatic metastatic prostate cancer, which can not be treated not hormone therapy (castration) * MAb used for diagnostic tests and radiologic imaging may be used, are not included ANCA = antineutrophil cytoplasmic antibody; CD = cluster of differentiation; CLL = chronic lymphocytic leukemia; CTLA = cytotoxic T lymphocyte antigen; Fc = crystallizable fragment; G-CSF = granulocyte-colony stimulating factor, GM-CSF = granulocyte-macrophage colony stimulating factor; HHV-8 = human herpes virus 8; ICAM = ICAM; IFN = interferon; mAb = monoclonal antibody, TNF = tumor necrosis factor. Monoclonal Antibodies Monoclonal antibodies (mAbs) can be produced in vitro for detection of specific target antigens. They are used for the treatment of solid and hematopoietic tumors and inflammatory diseases. Monoclonal antibodies are currently in clinical use Murine Chimeric Humanized For the production of murine mAb is a mouse immunized with an antigen (Ag) to recover from its spleen plasma cells that form specific antibodies against the injected Ag. Then, this Ak-producing cells are fused with immortal potentially mouse myeloma cells and cultured hybridoma cells (eg. As in cell cultures) to Ak-extraction. Although mouse antibodies are similar to human antibodies, the clinical use of mouse mAbs due to the production of human anti-mouse Akn is limited. You can (a type III hypersensitivity reaction) cause an immune complex serum sickness and are rapidly eliminated. An exception is muromonab-CD3 (OKT3), which effectively prevents acute rejection of a solid organ transplant; usually it is a patient who still receives other immunosuppressants, only once or twice administered (Overview transplantation: monoclonal antibodies). To minimize the problems caused by the use of pure mouse antibodies, researchers have recombinant DNA techniques for the development of monoclonal antibodies used, some of which are man-made and partly by the mouse. Depending on the proportion of the Ak molecule is of human origin, the resulting product is referred to in one of two ways: Chimeric Humanized In both cases, the process generally, as above, with the production of mouse hybridoma cells begins develop antibodies to the desired antigen. The DNA is then merged some or all variable parts of the mouse antibody with DNA for human immunoglobulin. The resulting DNA is in a mammalian cell culture, which then produces the resulting gene that produces the desired antibody. When the mouse gene is linked to the entire variable region with a human constant region, the product is called “chimera”. When the mouse gene is used only for the Ag-binding hypervariable regions of the variable region, the product is called “humanized”, yet more human. The chimeric mAbs activate antigen presenting cells (APC) and T cells more effectively than murine mAbs, but the production of human anti-chimeric Ab can still induce. Humanized mAb against various antigens (Ag) are approved to treat colon and breast cancer, leukemia, allergies, autoimmune diseases, transplant rejection, and respiratory syncytial virus infection. Fusion proteins These hybrid proteins can be combined generated by linking the gene sequences that encode all or a portion of 2 different proteins in order to generate a chimeric polypeptide, the desirable properties of the parent compounds having (z. B. a cell-target component with a cytotoxin ). The half-life of therapeutic proteins in the bloodstream can often (for example, the Fc region of IgG) be extended by fusion to another protein that occurs naturally has a longer serum half-life. Soluble cytokine receptors soluble versions of cytokine receptors are used as therapeutic reagents. By connecting to cytokines they can block their effects before they attach themselves to their normal cell surface receptor. Etanercept, a fusion protein that consists of 2 identical chains of CD120b receptor for tumor necrosis factor (TNF) -?. This ingredient blocked TNF-? and finds application in the treatment of refractory rheumatoid Arthrititis (RA), ankylosing spondylitis, psoriatic arthritis and plaque psoriasis. Soluble IL-receptors (eg. As those for IL-1, IL-2, IL-4, IL-5 and IL-6) are being developed for the treatment of inflammatory and allergic reactions as well as for cancer. Recombinant cytokines with colony stimulating factors (CSF) such as erythropoietin, granulocyte-CSF (G-CSF) and granulocyte-macrophage CSF (GM-CSF) are treated, undergoing chemotherapy or transplantation for hematological diseases and cancer patients (see table: some immunotherapeutics in clinical use *). Interferon-? (IFN-?) and IFN-? are used in the treatment of cancer, immune deficiency diseases and viral infections; IFN-? also in relapsing multiple sclerosis. Many other cytokines are still under investigation. Anakinra, a slightly modified form of the naturally occurring IL-1R antagonist, is used for the treatment of RA; it binds to the IL-1 receptor, thus preventing the binding of IL-1, but unlike IL-1, it does not activate the receptor. Cells expressing cytokine receptors may be target cells for modified versions of the corresponding cytokine (z. B. denileukin diftitox, a fusion protein with sequences of IL-2 and of diphtheria toxin). Denileukin is applied on the T-cell lymphoma of the skin, to attack the cell toxin expressing the CD25 component of the IL-2 receptor. Small molecule mimetics of small linear peptides annular peptides and small organic molecules have been developed as agonists or antagonists for different applications. Screening with series of peptides and organic compounds can be identified potential mimetics (z. B. agonists for receptors for erythropoietin, thrombopoietin, and G-CSF). Cell therapies immune system cells are harvested (for. Example, by Leukaphorese) and activated in vitro before they are returned to the patient. The goal is to strengthen the usually insufficient immune response to prostate cancer. The means of activation of immune cells includes the increase in the number of cytotoxic anti-tumor T-cells and their stimulation by cytokines and the pulsed exposure to antigen-presenting cells, such as dendritic cells with tumor antigens.

Health Life Media Team

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