| Description |
BT7480 (BCY11863) is one of the Bicycle tumor-targeted immune cell agonists (Bicycle TICAs). BT7480 is an angonist of CD137 (4-1BB). BT7480 consists of a poly(ethylene glycol) (PEG)-based linker, and a synthetic Bicycle peptide targeting CD137 conjugated to Bicycles targeting Nectin-4. Nectin-4 is a cell adhesion molecule, overexpressing in multiple tumor cells. BT7480 elicits significant CD137 agonism and potent antitumor activity in syngeneic mouse models[1][2].
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| Related Catalog |
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| Target |
CD137 (4-1BB)[1]
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| In Vitro |
BT7480 导致原代人免疫细胞中促炎细胞因子 IFNγ 和 IL-2 的分泌呈剂量依赖性增加 (EC50=0.22 nM 和 0.36 nM)，而 HT1376 肿瘤细胞与来自健康供体的人外周血单核细胞 (PBMC) 共培养并用抗 CD3 处理以刺激 CD137 在免疫细胞上的表达[1]。
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| In Vivo |
BT7480（5 mg/kg；腹腔注射；每天一次，持续 10 天）在 CT26-Nectin-4/huCD137 小鼠模型中表现出抗肿瘤活性[1]。 BT7480（2 mg/kg；静脉注射；单剂量）的 CL 为 8.5 mL/min/kg，终末半衰期为 3.6 小时[1]。 BT7480（1、5、10 和 30 mg/kg；腹腔注射；单剂量）导致 CD-1 小鼠的暴露量 (AUCinf) 剂量依赖性增加[1] 。 BT7480（1 和 10 mg/kg；腹腔注射；每天 3 次，持续 40 天）在小鼠 MC38-Nectin-4 肿瘤模型中导致肿瘤消退[1]。 在食蟹猴 MC38 同基因模型中的药代动力学分析[1] Route Dose (mg/kg) CLlast (mL/min/kg) Vdss (L/kg) t1/2 (h) i.v. 1 3.3 0.62 5.3 Animal Model: Mice bearing subcutaneous MC38-Nectin-4 tumors[1] Dosage: 1 mg/kg and 10 mg/kg Administration: IP; 3 times per days for 40 days Result: Led efficacious tumor growth reduction and complete responses (CRs) induction, with the rate of CRs ranging from 4/6 (1 mg/kg) to 6/6 (10 mg/kg) by day 40.
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| References |
[1]. Upadhyaya P, et al. Discovery and Optimization of a Synthetic Class of Nectin-4-Targeted CD137 Agonists for Immuno-oncology. J Med Chem. 2022 Jul 28;65(14):9858-9872. [2]. Hurov K, et al. A novel fully synthetic dual targeted Nectin-4/4-1BB Bicycle (R) peptide induces tumor localized 4-1BB agonism[J]. J. Immunother. Cancer, 2019, 7.
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