83-5980-63　Complement protein C5, Eculizumab Biosimilar 100ug　052008

特徴

• Eculizumab biosimilar is a recombinant humanized monoclonal IgG2/4κ antibody produced by Chinese hamster ovary cell culture and purified by standard bioprocess technology.
• Eculizumab biosimilar contains human constant regions from human IgG2 sequences and human IgG4 sequences and murine complementarity-determining regions grafted onto the human framework light- and heavy-chain variable regions.
• Eculizumab biosimilar is composed of two 448 amino acid heavy chains and two 214 amino acid light chains and has a molecular weight of ~148kD.
• Eculizumab is a recombinant humanized monoclonal antibody directed against the complement protein C5.
• The complement system pathways are the first line of defense against infectious threats.
• Their activation plays a critical role in innate and adaptive immune responses.
• Unfortunately, deregulations within the system have been shown to drive severe immune and inflammatory disorders.
• Eculizumab obtained the orphan drug status in 2003 and was approved in 2007 as the first drug targeting the complement system.
• It is now used for the treatment of paroxysmal nocturnal hemoglobinuria (PNH), atypical hemolytic uremic syndrome (aHUS), and refractory generalized myasthenia gravis (gMG).
• Here are some examples of eculizumab’s latest research.
• In February 2020, Vo et al.
• published the results of a pilot trial investigating the benefit of eculizumab for patients who received sustained transfusions and developed human leukocyte antigen (HLA) alloimmunization with severe thrombocytopenia.
• According to previous data, activation of the complement system plays a critical role in the destruction of platelets bound by HLA alloantibodies and may lead to platelet refractoriness.
• In this study, the authors suggested that eculizumab, with its ability to bind and inhibit the C5 complement, could be beneficial for such patients.
• The trial included 10 patients who received a single infusion of eculizumab.
• Interestingly, the four patients who responded well to the treatment showed higher post-transfusion platelet increments even 14 days after treatment.
• This study stands now as proof of principle for a larger scale trial evaluating the potential benefit of eculizumab for the treatment of platelet transfusion refractoriness.
• At around the same time, another study focused on complement-mediated disorders associated with poor outcomes such as C3 glomerulopathies (C3G) and primary immune complex-mediated membranoproliferative glomerulonephritis (IC-MPGN).
• A total of 10 patients were treated with eculizumab in two 48-week treatment stages separated by a washout period of 12 weeks.
• Three patients achieved proteinuria remission associated with kidney function stabilization.
• The authors also observed an eculizumab-mediated decrease of microangiopathy that was associated with better clinical outcomes for patients with IC-MPGN.
• Thrombotic microangiopathy (TA-TMA), caused by an overactivated complement system, is also associated with poor outcomes for hematopoietic stem cell transplant (HSCT) recipients.
• In January 2020, Jodele et al.
• published a study including 64 pediatric HSCT recipients with a high risk of developing TA-TMA and multi-organ injury.
• Patients treated with eculizumab showed significant survival rate improvement (66%) one year after transplant compared to an untreated cohort sharing the same characteristics (16.7%).
• During the treatment process, the authors found that the number of eculizumab doses had to be adapted to the level of therapeutic response of each patient.
• Patients with higher levels of complement activation as well as intestinal bleeding had a lower response to treatment, required more doses of eculizumab, and their one-year survival was lower (44% vs 78%, p=0.01).
• The study concluded that the inhibition of an overactivated complement with eculizumab could be an effective strategy for most pediatric HSCT patients with high-risk TA-TMA.
• However, it is still critical to find other early treatment options for patients with the most severe cases of disease.
• Applications:Suitable for use in Functional Assays.
• Other applications not tested.
• Recommended Dilution:Optimal dilutions to be determined by the researcher.
• Storage and Stability:May be stored at 4℃ for short-term only.
• Aliquot to avoid repeated freezing and thawing.
• Store at -20℃.
• Aliquots are stable for 12 months after receipt.
• For maximum recovery of product, centrifuge the original vial after thawing and prior to removing the cap.