Human IL-3Rα (CD123) Antibody - Talacotuzumab Biosimilar

Anti-human IL-3R alpha - Talacotuzumab biosimilar - CAS #1826831-79-1

Binding of Anti-IL-3R Talacotuzumab

Anti-hIL-3R-hIgG1-DE is a biosimilar antibody of Talacotuzumab, a human interleukin 3 receptor alpha subunit (IL-3Rα, CD123) antibody that blocks IL-3 signaling. This monoclonal antibody (mAb) has reached phase 2/3 in a clinical trial to treat patients with acute myeloid leukemia (AML).

 More details

Anti-hIL-3R-hIgG1-DE comprises the variable region of Talacotuzumab and the IgG1 constant region of Talacotuzumab mediating high effector functions. 

This antibody can be used together with HEK-Blue™ IL-3 cells for screening and neutralization assays to block IL-3R signaling induced by recombinant human IL-3 (see figure).

Key features

• Each lot is functionally tested and validated.
• The complete sequence of the antibody construct was verified.
• The absence of endotoxins is determined by the EndotoxDetect™ assay.

All InvivoGen products are for internal research use only, and not for human or veterinary use.

Figures

Dose-dependent inhibition of HEK-Blue™ IL-3 cell response using Talacotuzumab biosimilar. Increasing concentrations of Anti-hIL-3Rα Talacotuzumab biosimilar (30 ng/ml - 30 µg/ml) were incubated with HEK-Blue™ IL-3 cells for 1 h before the addition of recombinant human IL-3 (100 pg/ml). After overnight incubation, SEAP activity in the cell culture supernatant was assessed using QUANTI-Blue™ Solution. Data are shown in percentage of activity (mean ± SEM).

Specifications

Application: Neutralization assay, ELISA, ADCC

Isotype:  Human IgG1 (S239D/I332E), kappa

Recommended isotype control: Human IgG1

Target: Human IL-3Rα (CD123)

Species reactivity: Human

Clone: Talacotuzumab, JNJ-56022473, CSL-362, CSL362

Cas number: 1826831-79-1

Sterility: 0.2 µm filtration

Source: CHO cells 

Production: Animal-free

Purification: Protein A

Molecular weight: 148 kDa

Physical form: Lyophilized

Formulation buffer: Sodium phosphate buffer with glycine, saccharose, and stabilizing agents

Preservative: Azide-free

Reconstitution buffer: Sterile water (not provided)

Purity: ≥ 95 %

Quality control: Each lot is functionally tested and validated.

Contents

Anti-hIL-3R-hIgG1-DE purified monoclonal antibody is provided azide-free and lyophilized. It is available in two quantities:

• hil3r-mab18: 100 µg
• hil3r-mab18-03: 3 x 100 µg

 The product is shipped at room temperature.

 Upon receipt, store lyophilized antibody at -20 °C.

 Lyophilized antibody is stable for up to 1 year.

 Avoid repeated freeze-thaw cycles.

Details

Talacotuzumab (JNJ-56022473, CSL-362) background

Talacatozumab is a therapeutic, humanized monoclonal antibody (mAb) that targets the human IL-3 receptor alpha subunit (CD123) of the IL-3 receptor [1]. It acts like a receptor antagonist and inhibits IL-3 intracellular signaling [1]. Talacotuzumab was engineered to feature the S239D/I332E double mutation in the Fc region to enhance the binding to CD16 (FcgRIIIa) on the surface of NK cells, to increase the antibody-dependent cellular cytotoxicity (ADCC) [1]. CD123 is overexpressed in multiple hematologic cancers, especially in leukemic stem cells. It is considered an important biomarker of high-risk disease characteristics in acute myeloid leukemia (AML) [2]. Although Talacotuzumab demonstrated promising activity in AML patients [3], later phase 2/3 clinical studies pointed to considerable toxicity [4].

References:

1. Busfield, S.J. et al., 2014. Targeting of acute myeloid leukemia in vitro and in vivo with an anti-CD123 mAb engineered for optimal ADCC. Leukemia. 28(11):2213-2221.
2. Chen Y., et al., 2023. A perspective of immunotherapy for acute myeloid leukemia: Current advances and challenges. Front Pharmacol. 14: 1151032.
3. Xie, L.H. et al., 2017. 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 7(6):e567.
4. Montesinos P., et al., 2021. Safety and efficacy of talacotuzumab plus decitabine or decitabine alone in patients with acute myeloid leukemia not eligible for chemotherapy: results from a multicenter, randomized, phase 2/3 study. Leukemia 35, 62–74.