CD40 is a transmembrane glycoprotein. CD40 can express on B cells and antigen presenting cells (APCs) such as monocytes, macrophages, and dendritic cells (DC). It also expresses on platelets. Furthermore,  CD154, CD40 ligand, or CD40L are the ligand of CD40. For example, the Binding of CD154 to CD40 can induce signaling via NF-κB, and MAPK pathways. Then regulates cell proliferation, survival, and differentiation. Today, we will introduce an IGg1 monoclonal antibody (mAb) targeting CD40 — Iscalimab.

Iscalimab (CFZ-533) is an IGg1 mAb Targeting CD40 for Inflammation Research

Iscalimab (CFZ533) is a nondepleting anti-CD40 antibody. It can be used for the inhibition of transplant organ rejection and the research of autoimmune diseases. Firstly, Iscalimab can bind CD40 on B cells from humans, rhesus, and cynomolgus animals with EC₅₀ values of approximately 0.2 μg/mL.

In vitro, Iscalimab (0.01-1 μg/mL, overnight) blocks rCD154-induced TNF production by primary monocyte-derived dendritic cells (moDCs), with an IC₅₀ of 0.04 μg/mL. Meanwhile, Iscalimab (3 days) can inhibit rCD154-induced proliferation of PBMCs from humans, rhesus, and cynomolgus animals with IC₅₀s of 0.02, 0.03, and 0.01 μg/mL, respectively. Also, Iscalimab (2 μg/mL, 3 h) is internalized by B cells in a CD40-dependent manner. In vivo, Iscalimab (150 mg/kg/week, s.c, for 13 weeks) is well tolerated and does not cause any dose-limiting toxicity in rhesus monkeys. At the same time, Iscalimab (10 mg/kg, i.v.) completely inhibits T cell-dependent antibody response in Rhesus monkeys. Furthermore, Iscalimab (30 mg/kg, i.v.) prolongs allograft survival in kidney transplant cynomolgus.

In conclusion, Iscalimab (CFZ-533) is a non-depleting IGg1 monoclonal antibody targeting CD40. Iscalimab can be used for the research of autoimmune diseases.

Reference:

[1]  Kahaly GJ, et al. J Clin Endocrinol Metab. 2020 Mar 1;105(3):dgz013.

[2]  Flandre TD, et al. Toxicol Pathol. 2022 Jul;50(5):712-724.

[3]  Ristov J, et al. Am J Transplant. 2018 Dec;18(12):2895-2904.

[4]  Cordoba F, et al. Am J Transplant. 2015 Nov;15(11):2825-36.

[5]  Henry Velazquez Soto, et al. World Journal of Immunology. January 2022.12(1):1-8