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

Human

IL-3Ra/CD123

Talacotuzumab (JNJ 56022473; CSL 362) strongly mediates ADCC of TF-1 cells with an ic50 of 5 ng/ml (33 pM)^[1].
Talacotuzumab (1 μg/ml; pretreatment for 24 hours) inhibits TLR7-stimulated (Imiquimod; HY-B0180; 0.5 μM; for 6 days) and TLR9-stimulated (CpG C; 0.5 μM; for 6 days) IFN-α production in both SLE donors and healthy donors plasmacytoid dendritic cells (pDCs) and basophils, whereas TLR4-stimulated (LPS; HY-D1056; 10 μg/ml) production is not significantly reduced. Talacotuzumab inhibits TLR7- and TLR9-induced plasmablast expansion and proliferation by depletion of plasmacytoid dendritic cells (pDCs)^[2].

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

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  Human IgG1 kappa

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  Immobilized IL-3R alpha/CD123 Protein, Human can bind Talacotuzumab. The EC₅₀ for this effect is 6.855 ng/mL.
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  Flow cytometric analysis of 1.5X10⁶ THP-1 cells labeling Talacotuzumab (HY-P99395, red). Cells were fixed with 4% paraformaldehyde. Then stained with the primary antibody at 1/200 dilution for an hour at 4℃. Goat Anti-Human IgG H&L (AF488) (HY-P83776) was used as the secondary antibody at 1/1,000 dilution for 30 minutes at 4℃. Human IgG1 kappa (HY-P99001, blue) was used as the isotype control, cells without incubation with primary antibody were used as the unlabeled control (black).

• [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]