Ruplizumab Biosimilar, Anti-human CD40L Monoclonal Antibody

Ruplizumab Biosimilar uses the same protein sequences as the therapeutic antibody ruplizumab. Ruplizumab is a humanized anti-CD40L/CD154 monoclonal antibody. he binding of CD40 to its ligand, CD40L, is a critical element in T cell activation. In systemic lupus erythematosus, CD40L is over-expressed on T cells, B cells, and monocytes. It was intended for the treatment of rheumatic diseases like systemic lupus erythematosus and lupus nephritis, as well as the primary skin allograft rejection. A study showed that the drug was associated with life-threatening thromboembolisms, while another study only found thrombocytopenia. In previous studies, the monoclonal antibody, ruplizumab showed evidence of potential efficacy in patients with lupus nephritis and idiopathic thrombocytopenic purpura. Besides, clinical trials were halted because of a higher than expected occurrence of thromboembolic events. It is proposed that the observed treatment-related (TR) thromboembolic events occurred as a result of platelet activation and aggregation, due to the formation of anti-CD40L antibody and soluble CD40L immune complexes that tether to platelets via binding of sCD40L to surface-expressed CD40 and activate platelets through interactions of the Fc with Fc gamma receptor IIA on the platelet surface. Modern allotransplantation requires the daily administration of nonspecific immunosuppressive agents to prevent T cell-mediated acute rejection. The agents commonly used include glucocorticosteroids, antiproliferative agents such as azathioprine or mycophenolate mofetil (MMF) and calcineurin inhibitors (tacrolimus or cyclosporine A). Although these agents have considerably improved the outcome of patients receiving solid organ transplants, their therapeutic effects are transient, and all are associated with substantial toxicity. The CD40 ligand (CD40L, also known as CD154) has been shown to be an important modulator of immunoinflammatory events in autoimmune disease and acute allograft rejection. CD40 is expressed constitutively on antigen presenting cells (APCs), including B cells, while CD40L is a member of the tumor necrosis factor family of transmembrane glycoproteins and is expressed on activated CD4? T cells. The CD40-CD40L interaction is essential for normal T cell?B-cell interactions, including T-cell priming, immunoglobulin (Ig) class-switching, and the T cell-dependent humoral immune response. Indeed, the CD40-CD40L molecules form a co-stimulatory pair, providing the second signal required for T-cell activation of APCs. CD154 binds to CD40 and leads to APC secretion of IL-1?, TNF-?, and IL-12, and to endothelial cell secretion of monocyte chemotactic factors. It also increases APC and endothelial cell expression of MHC class II molecules, of adhesion molecules, and of the co-stimulatory ligands CD80 and CD86. Although blockade of the CD154-CD40 pathway does little to prevent the proliferative response of CD4+ T cells in vitro, it substantially curtails the maturation of cytotoxic CD8+ T cells by interfering with required T-cell-APC interactions. The monoclonal antibody ruplizumab neutralizes CD40L function, as it blocks the interaction between CD40 and CD40L. It has been proven in animal experiments that this drug can prolong rhesus monkey renal allograft survival.

Product Details
Species Reactivity	Human
Source	Mammalian cells
Host/Isotype	Human IgG1 kappa
Class	Monoclonal
Type	Antibody
Immunogen	The human CD40L
Clone	Ruplizumab Biosimilar
Conjugate	Unconjugated
Purity	>95%
Molecular Weight	145.68 kDa
Protein Concentration	1 mg/ml
Formulation	Liquid
Storage Condition	4°C for short time, -20°C or -80°C for long time.
Storage Buffer	0.2 uM filtered PBS solution, pH 7.4