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编 号:F747435
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Talacotuzumab (JNJ 56022473; CSL 362) is an IgG1-type fully humanized, CD123-neutralizing monoclonal antibody containing a modified Fc structure. Talacotuzumab has KDs of 0.43 nM, 188 nM, 46 nM, 16.8 nM for CD123, CD32b/c, CD16-158F, CD16-158V, respectively. Talacotuzumab inhibits IL-3 binding to CD123, antagonizing IL-3 signaling in target cells. Talacotuzumab has mutated the Fc region to increase affinity for CD16 (FcγRIIIa), thereby enhancing antibody-dependent cell-mediated cytotoxicity (ADCC). Talacotuzumab is highly effective in vivo reducing leukemic cell growth in acute myeloid leukemia (AML) xenograft mouse models.

体内研究:
塔妥珠单抗 (JNJ 56022473; CSL 362; 300 μg; 腹腔注射; 每周三次持续 5 周) 与同种型对照相比,在急性髓性白血病小鼠异种移植物中导致肿瘤生长显着延迟。塔妥珠单抗 (1, 10, 30 mg/kg; 皮下注射; 单次注射) 在幼稚食蟹猴中以 1、10、30 mg/kg 的剂量在 48 小时最大血清浓度分别为 12、190 和 380 μg/ml。Animal Model:Nonobese diabetic/severe combined immunodeficiency mice injected intravenously AML xenograft cells (AML-5)
Dosage:300 μg
Administration:IP; thrice weekly for 5 weeks
Result:Resulted in a significant delay in tumor growth compared with an isotype control.

体外研究:
塔妥珠单抗 (JNJ 56022473; CSL 362) 强烈介导 TF-1 细胞的抗体依赖性细胞介导的细胞毒性 (ADCC),IC50 为 5 ng/ml (33 pM)。塔妥珠单抗 (1 μg/ml; 预处理 24 小时) 抑制 SLE 供体和健康供体浆细胞样树突状细胞和嗜碱性粒细胞中 TLR7 刺激 (咪喹莫特; HY-B0180; 0.5 μM; 6 天) 和 TLR9 刺激 (CpG C; 0.5 μM; 6 天) IFN-α 的产生,而 TLR4 刺激 (LPS; HY-D1056; 10 μg/ml) IFN-α 的产生没有显着减少。塔妥珠单抗通过耗尽浆细胞样树突状细胞 (pDC) 来抑制 TLR7 和 TLR9 诱导的浆母细胞扩增和增殖
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