Tarlatamab (AMG-757) 是一种双特异性 T 细胞接合剂 (BiTE) 抗体，靶向 delta 样配体 3 (DLL3)。DLL3 是在小细胞肺癌 (SCLC) 肿瘤中选择性表达的靶标，但在正常组织中表达很少。Tarlatamab 对人和非人灵长类动物 (NHP) 的 DLL3 的KD分别为 0.64 nM 和 0.50 nM，对 CD3 的KD分别为 14.9 nM 和 12 nM。Tarlatamab 是针对 DLL3 的一流 HLE BiTE 免疫肿瘤疗法，具有用于 SCLC 研究的潜力。
| 生物活性 | Tarlatamab (AMG-757) is a bispecific T-cell engager (BiTE) antibody targetingdelta-likeligand 3 (DLL3). DLL3 is a target that is selectively expressed in small-cell lungcancer(SCLC) tumors, but with minimal normal tissue expression. Tarlatamab has theKDs of 0.64 nM and 0.50 nM for human and nonhuman primate (NHP) DLL3, respectively. Tarlatamab has theKDs of 14.9 nM and 12 nM for human and NHP CD3, respectively. Tarlatamab is a first-in-class HLE BiTE immuno-oncology therapy targeting DLL3 and has the potential for SCLC research[1]. |
体外研究
(In Vitro) | Tarlatamab (AMG-757; 0-10 nM; 48 小时) 在体外对表达 DLL3 的 SCLC 细胞系具有有效的特异性细胞毒活性[1]。
Tarlatamab (0-10 nM; 4-72 小时) 随时间增加颗粒酶 B 水平和细胞毒性，在 48 小时观察到最大信号。T 细胞活化或炎症标志物 CD69、CD71、PD-1 和 PD-L1 (37-39) 被上调[1]。
Cell Viability Assay[1] | Cell Line: | SCLC cell lines (DMS 79, NCI-H2171, NCI-H889, SHP-77, NCI-H211,COR-L279) | | Concentration: | 0-10 nM | | Incubation Time: | 48 hours | | Result: | AMG 757 effectively engaged human T cells to kill SCLC cell lines, including those with very low DLL3 expression levels. |
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体内研究
(In Vivo) | Tarlatamab (AMG-757; 3 mg/kg; 腹腔给药; 每周一次; 连续三周) 在 SCLC 小鼠模型中驱动肿瘤消退[1]。
Tarlatamab (12 μg/kg; 腹腔给药; 单剂量) 在非人灵长类动物 (NHP) 的平均半衰期为 234 小时 (9.8 天)，平均清除率为 0.487 mL/hour/kg，稳态分布容积为 146 mL/kg[1]。
| Animal Model: | Female NOD.Cg-PrkdcscidIl2rgtm1Sug/JicTac (NOG) mice with patient-derived SCLC tumor fragments (LXFS 1129 and LXFS 538)[1] | | Dosage: | 3 mg/kg | | Administration: | IP; once weekly for 3 weeks | | Result: | Led to 83% tumor regression and an overall significant reduction in tumor volume compared with that in mice which received a control HLE BiTE molecule in the LXFS 1129 model.
Induced 98% tumor regression in the LXFS 538 model. |
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| 储存方式 | Please store the product under the recommended conditions in the Certificate of Analysis. |
