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Letolizumab (BMS-986004) is a monoclonal antibody 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]. | [in vivo]
Letolizumab inhibits the viability of CD40L trimer and CHO-CD40L in human B cell (IC50 values of 3.6 nM and 1.3 nM, respectively) or nonhuman primate B cell (IC50 values of 3.8 nM and 7.3 nM, respectively)[2].
Letolizumab (2, 10 and 20 mg/kg; i.v.; once a week for 10 weeks) prolongs the survival time of rhesus macaques after renal transplantation[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. |
| [IC 50]
CD40L | [References]
[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. DOI:10.1016/j.addr.2018.12.005
[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. DOI:10.1111/ajt.14197
[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. DOI:10.1080/13543784.2019.1557146 |
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