Talacotuzumab (JNJ 56022473) is an IgG1 fully humanized CD123 neutralizing monoclonal antibody containing a modified Fc structure. Talacotuzumab has a high affinity for CD123, CD32b/c, CD16-158F and CD16-158V, with KD of 0.43 nM, 188 nM, 46 nM and 16.8 nM, respectively. Talacotuzumab inhibits IL-3 signaling in target cells by inhibiting IL-3 binding to CD123. Talacotuzumab induces mutations in the Fc region to increase affinity for CD16 (FCγriiia), thereby enhancing antibody-dependent cell-mediated cytotoxicity (ADCC). Talacotuzumab inhibits leukemia cell growth in xenografted mouse models of acute myeloid leukemia (AML).

TF-1 cells:33 pM

Talacotuzumab（JNJ 56022473; CSL 362）以 IC50 为 5 ng/ml（33 pM）的浓度，强效地介导针对TF-1细胞的抗体依赖性细胞介导的细胞毒性（ADCC）[1]。在1 μg/ml的浓度下预处理24小时后，Talacotuzumab 能够抑制SLE（系统性红斑狼疮）捐献者及健康捐献者的浆样树突状细胞和嗜酸性粒细胞产生IFN-α，这种抑制作用出现在这些细胞受到 TLR7（imiquimod; 0.5 μM; 6天）和TLR9（CpG C; 0.5 μM; 6天）刺激时。然而，Talacotuzumab 并不显著减少由TLR4刺激（LPS; 10 μg/ml）引起的IFN-α产生。通过耗尽pDC，Talacotuzumab 对由TLR7和TLR9引起的浆样树突细胞（pDC）增殖和扩张的抑制效果得以实现[2]。

在带有急性髓性白血病异种移植物的小鼠中，Talacotuzumab（JNJ 56022473; CSL 362; 300 μg; 腹腔注射; 每周三次，连续5周）与同型对照相比，显著延缓了肿瘤生长[1]。在青年猕猴中，Talacotuzumab（1, 10, 30 mg/kg; 皮下注射; 单剂量）在1、10和30 mg/kg的剂量下，分别在48小时内达到最大血清浓度12、190和380 μg/ml [2]。