Letolizumab

Letolizumab (BMS-986004) is a dimer antibody construction targeting CD40L, which is produced to express mutant IgG1 lacking effector function, including Fc binding and complement fixation. Letolizumab reduces rejection, thromboembolism and prolongs the survival time[1][2][3].

Research Areas >> Inflammation/Immunology

CD40L

Letolizumab 降低了恒河猴肾移植后的排斥反应和 CCR7-CD45RA+ CD4+ T 细胞终末分化，当与巴利昔单抗 (Basiliximab，HY-108852)、吗替麦考酚酯 (Mycophenolate mofetil，HY-B0199) 和类固醇联合使用时[2]。 Letolizumab 抑制 CD40L 三聚体和 CHO-CD40L 在人类 B 细胞 (IC50 值分别为 3.6 nM 和 1.3 nM) 或非人类灵长类 B 细胞 (IC50 值分别为 3.8 nM 和 7.3 nM) 中的活力[2]。 Letolizumab (2、10 和 20 mg/kg；静脉注射；一周一次持续 10 周) 延长了肾移植后的恒河猴的存活时间[2]。 Animal Model: Rhesus macaques after renal transplantation[2]. Dosage: 2, 10 and 20 mg/kg. Administration: Intravenous injection; once a week for 10 weeks. Result: Increased the survival time.

[1]. Karnell JL, et al. Targeting the CD40-CD40L pathway in autoimmune diseases: Humoral immunity and beyond. Adv Drug Deliv Rev. 2019 Feb 15;141:92-103.  

[2]. Kim SC, et al. Fc-Silent Anti-CD154 Domain Antibody Effectively Prevents Nonhuman Primate Renal Allograft Rejection. Am J Transplant. 2017 May;17(5):1182-1192.  

[3]. Spicer P, et al. Costimulatory pathway targets for autoimmune and inflammatory conditions: clinical successes, failures, and hope for the future. Expert Opin Investig Drugs. 2019 Feb;28(2):99-106.