Talacotuzumab  (Synonyms: 塔妥珠单抗; JNJ 56022473; CSL 362)

Talacotuzumab (JNJ 56022473; CSL 362) is an IgG1-type fully humanized, CD123-neutralizing monoclonal antibody containing a modified Fc structure. Talacotuzumab has K_Ds 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^[1][2][3][4].

Human IgG1 kappa

Human IgG1 kappa, Isotype Control

Humanized

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)^[1]。
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^[2]

MCE has not independently confirmed the accuracy of these methods. They are for reference only.

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^[1]。
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^[2]。

MCE has not independently confirmed the accuracy of these methods. They are for reference only.

1826831-79-1

液体

Colorless to light yellow

塔妥珠单抗

Shipping with dry ice.

Please store the product under the recommended conditions in the Certificate of Analysis.

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  Human IgG1 kappa

• [1]. S J Busfield, et al. Targeting of acute myeloid leukemia in vitro and in vivo with an anti-CD123 mAb engineered for optimal ADCC. Leukemia. 2014 Nov;28(11):2213-21.  [Content Brief]

  [2]. Shereen Oon, et al. A cytotoxic anti-IL-3Rα antibody targets key cells and cytokines implicated in systemic lupus erythematosus. JCI Insight. 2016 May 5;1(6):e86131.  [Content Brief]

  [3]. Erwin M Lee, et al. Efficacy of an Fc-modified anti-CD123 antibody (CSL362) combined with chemotherapy in xenograft models of acute myelogenous leukemia in immunodeficient mice. Haematologica. 2015 Jul;100(7):914-26.  [Content Brief]

  [4]. L H Xie, et al. CD123 target validation and preclinical evaluation of ADCC activity of anti-CD123 antibody CSL362 in combination with NKs from AML patients in remission. Blood Cancer J. 2017 Jun 2;7(6):e567.  [Content Brief]