Human CD40L Antibody - Frexalimab Biosimilar

Anti-human CD40L - Frexalimab biosimilar - CAS #2515463-86-0

Binding of Anti-hCD40L Frexalimab

Anti-hCD40L-hIgG1 is a biosimilar antibody of Frexalimab, a human CD40 ligand (CD40L) antibody that specifically blocks the binding between CD40L to its receptor CD40. This monoclonal antibody (mAb) shows promising results across multiple trials in treating various autoimmune diseases, such as relapsing multiple sclerosis, alleviating fatigue in primary Sjögren’s syndrome, and improving glycemic control in diabetic patients.

 More details

Anti-hCD40L-hIgG1 comprises the variable region of Frexalimab and the IgG1 constant region of Frexalimab, mediating high effector functions. 

This antibody can be used together with HEK-Blue™ CD40L cells for screening and neutralization assays to block CD40L signaling induced by recombinant human CD40L (see figure).

Key features

• Each lot is functionally tested and validated.
• The complete sequence of the antibody construct has been verified.
• The absence of endotoxins is determined by the EndotoxDetect™ assay.

All InvivoGen products are for internal research use only, and not for human or veterinary use.

Figures

Dose-dependent inhibition of HEK-Blue™ CD40L cell response using Frexalimab biosimilar. Increasing concentrations of Anti-hCD40L-hIgG1 (0.1 ng/ml - 3 µg/ml) were incubated with CHO-derived recombinant human CD40L (30 ng/ml) 1 hour prior to the addition of HEK-Blue™ CD40L cells. After overnight incubation, SEAP activity in the cell culture supernatant was assessed using QUANTI-Blue™ Solution. Data are shown as the percentage of activity (mean ± SEM).

Specifications

Application: Neutralization assay, ELISA

Isotype:  Human IgG1, kappa

Recommended isotype control: Human IgG1

Target: Human CD40L

Species reactivity: Human

Clone: Frexalimab, SAR441344, INX-021

Cas number: 2515463-86-0

Source: CHO cells 

Production: Animal-free

Purification: Protein A

Molecular weight: 145.8 kDa

Physical form: Lyophilized

Formulation buffer: Sodium phosphate buffer with glycine, saccharose, and stabilizing agents

Preservative: Azide-free

Reconstitution buffer: Sterile water (not provided)

Purity: ≥ 95 %

Quality control: Each lot is functionally tested and validated.

Contents

Anti-hCD40L-hIgG1 purified monoclonal antibody is provided azide-free and lyophilized. It is available in two quantities:

• h40l-mab1: 100 µg
• h40l-mab1-03: 3 x 100 µg

 Upon receipt, store lyophilized antibody at -20 °C.

 The lyophilized product is stable for at least 1 year.

 Avoid repeated freeze-thaw cycles.

Details

Frexalimab and CD40L background

Frexalimab (SAR441344) is a second-generation monoclonal antibody targeting the CD40 ligand (CD40L). It is designed to specifically block the binding between CD40L and CD40 [1].

CD40 Ligand (CD40L), also known as CD154, TRAP, or gp39, is a type II transmembrane glycoprotein belonging to the tumor necrosis factor (TNF) family. It is mainly expressed in CD4+-T cells and interacts with CD40 on antigen-presenting cells to regulate both humoral and cellular immune responses [2-3]. The CD40 cytoplasmic domain binds directly to several TNF receptor-associated factors (TRAFs), and this interaction is thought to initiate CD40 signaling. CD40-mediated signaling results in NF-κB, c-Jun N-terminal kinase (JNK), and p38 mitogen-activated protein kinase (MAPK) activation.

CD40L-CD40 interactions are thought to play an important role in the pathogenesis of many diseases [5, 6]. Thus, blocking this interaction using agents, such as Frexalimab, has shown promising results across multiple trials in treating various autoimmune diseases, such as relapsing multiple sclerosis, alleviating fatigue in primary Sjögren’s syndrome, and improving glycemic control in diabetic patients [1]. 

1. Fatima T, et al., 2024. Frexalimab (SAR441344) as a potential multiautoimmune disorder tackling mAB targeting the CD40-CD40L pathway undergoing clinical trials: a review. Ann Med Surg (Lond). ;86(12):7305-7313.
2. Karnell J.L. et al., 2019. Targeting the CD40-CD40L pathway in autoimmune diseases: Humoral immunity and beyond. Adv Drug Deliv Rev. 141:92-103. 
3. Laman J.D. et al., 2017. Functions of CD40 and Its Ligand, gp39 (CD40L). Crit Rev Immunol. 37(2-6):371-420.
4. Elgueta R. et al., 2009. Molecular mechanism and function of CD40/CD40L engagement in the immune system. Immunol. Rev. 229, 152–172.
5. Seijkens T. et al., 2013. CD40–CD40L: Linking pancreatic, adipose tissue and vascular inflammation in type 2 diabetes and its complications. Diabetes and Vascular Disease Research. 10: 115-122.
6. Daoussis D. et al., 2004. Targeting CD40L: a promising therapeutic approach. Clin Diagn Lab Immunol. 11(4):635-41.