Infliximab

Infliximab 化学特性,用途語,生産方法

• 説明

  Infliximab is a chimeric (“humanized”) IgG1κ monoclonal antibody to human TNFα. By combining the Fv domain of the mouse antibody responsible for recognizing TNFα with parts of the human Fc domain of IgG1 (IgG1κ), the fused protein looks more like normal human IgG1 molecule (“humanized”), so there is a better chance the fused protein will not be destroyed by the patient's own immune system.

• 適応症

  Infliximab (Remicade), a chimeric anti-TNF monoclonal antibody, and adalimumab (Humira), a fully humanized anti-TNF monoclonal antibody, are both promising therapies under investigation for psoriasis.
  
  Infliximab is a chimeric monoclonal antibody targeted against TNF-α. It consists of a human IgG₁ Fc heavy chain and partial κ-light chain fused to a murine hypervariable region. Infliximab binds to both soluble and transmembrane forms of TNF-αand inhibits their ability to bind to TNF receptors. It does not inhibit TNF-β, which binds to the same receptors as TNF-α. Infliximab is administered intravenously, usually at 4 to 8-week intervals.

• 生物学の機能

  Infliximab is produced by a recombinant cell line cultured by continuous perfusion and is purified by a series of steps that includes measures to inactivate and remove viruses. Cells expressing transmembrane TNFα bound by infliximab can be lysed. The TNFα antibodies decrease synovitis and joint erosions in a murine model of collagen-induced arthritis and, when administered after disease onset, allows eroded joints to heal.

• 一般的な説明

  The MAb infliximab (Remicade, chimeric) is produced fromcells that have been sensitized with human TNFα. The MAbis a chimeric human–mouse immunoglobulin. The constantregions are of human peptide sequence and the variable regionsare murine. The MAb is of type IgG1 κ.
  Infliximab is indicated for the treatment of moderately toseverely active Crohn disease to decrease signs and symptomsin patients who had an inadequate response to conventionaltreatments. Infliximab binds specifically to TNFα. Itneutralizes the biological activity of TNFα by binding withhigh affinity to soluble and transmembrane forms of theTNF. Infliximab destroys TNFα-producing cells. An additionalmechanism by which infliximab could work is asfollows: by inhibiting TNFα, pathways leading to IL-1 andIL-6 are inhibited. These interleukins are inflammatory cytokines.Inhibiting their production blocks some of theinflammation common to Crohn disease.

• 生物活性

  Infliximab has an approximate molecular weight of 149,100 daltons and binds specifically, with high affinity, to both the transmembrane and soluble forms of TNFα in the blood, thus neutralizing its biological activity. It does not bind to TNFβ (lymphotoxin A), a related cytokine that uses the same receptors as TNFα.

• 臨床応用

  Infliximab (Remicade) is a mouse–human chimeric monoclonal neutralizing antibody to human TNF-αand is considered a biological drug. Specific indications are for the reduction of signs and symptoms in patients with moderately to severely active Crohn’s disease who have had an inadequate response to conventional therapies (single infusion) and for reduction of the number of draining enterocutaneous fistulas in patients with fistulizing Crohn’s disease (three-infusion regimen).

• 副作用

  Infliximab produces an acute infusion-related reaction consisting of fever and chills in approximately 20% of patients. Other common side effects include headache, nausea, and diarrhea. Persons given infliximab with methotrexate may have a greater elevation of hepatic enzyme levels than those given methotrexate alone. Because it is a human–mouse fusion protein, infliximab seems to be more immunogenic than etanercept. During infliximab treatment, autoantibodies (anti-dsDNA, ANA) and antibodies to the drug itself (human antichimeric antibodies) can develop. Concomitant therapy with methotrexate or immunosuppressive drugs decreases this risk somewhat. It is possible that infliximab may increase the incidence of autoimmune diseases and malignancies; however, longterm data are needed to determine whether this is the case.As with etanercept, a low risk of serious infection was seen in clinical trials of infliximab; however, sepsis, disseminated tuberculosis, and other potentially fatal infections have been reported in patients taking this drug.

• 予防処置

  Infliximab should not be given to individuals withknown hypersensitivity to murine proteins. As withetanercept, precautions for the prevention of serious infectionsmust be taken, and live virus vaccines are contraindicated.

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