Emirodatamab  (Synonyms: AMG-427)

Emirodatamab (AMG-427) is a bispecific T-cell engager (BiTE). Emirodatamab simultaneously binds FLT3 on the surface of acute myeloid leukemia (AML) cells and CD3 on the surface of T cells, thereby precisely recruiting immune effector cells to tumor sites. Emirodatamab potently induces T cell activation, secretion of proinflammatory cytokines (such as IFNγ, TNFα), and specific cytotoxicity, effectively lysing FLT3-positive tumor cells and inhibiting their growth. Emirodatamab not only significantly prolongs survival in mouse xenograft models and eliminates diseased cells in primates, but also exhibits a synergistic enhancement effect when combined with PD-1 blockade therapy. Emirodatamab is used in studies of acute myeloid leukemia, especially relapsed or refractory cases^{[1][2][3][4][5]}.

(scFv-heavy-kappa)-(scFv-heavy-lambda)-scFc

Human

CD3E & FLT3

Emirodatamab potently induces cytotoxicity in primary AML blasts with high FLT-3 expression under ex vivo conditions, and its activity is enhanced when combined with anti-PD-1 antibodies^[2].
Emirodatamab mediates in vitro killing of primary AML cells in a manner dependent on FLT3 expression levels and effector-to-target cell ratio, and its activity is enhanced when combined with anti-PD-1 antibodies^[4].
Emirodatamab induces potent, target-specific sub-picomolar TDCC effects in FLT3-expressing human AML cell lines, accompanied by T cell activation and cytokine secretion; it retains complete killing activity against target cells even in the presence of disease-relevant concentrations of sFLT3 or sFLT3L^[5].
Emirodatamab exhibits lower potency against PD-L1-expressing MOLM-13 AML cells compared to parental MOLM-13 AML cells^[5].

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

Emirodatamab (0.12-3 mg/kg; intravenous injection; once every 5 days; 6 doses total) significantly prolongs the survival of mice with orthotopic MOLM-13 AML xenografts, with the median survival time ranging from 36.5 to 42.5 days across all dose groups^[5].
Emirodatamab (0.01-1 mg/kg; intravenous injection; once every 7 days; 6 doses total) significantly prolongs the survival of mice bearing orthotopic EOL-1 AML xenografts^[5].
Emirodatamab (C_max=1-10 nM; intravenous injection; 3 administrations) dose-dependently eliminates FLT3-expressing hematopoietic progenitor cells in cynomolgus monkeys, reduces FLT3 transcript levels in bone marrow and blood by up to 97%, and induces T cell activation and cytokine release^[5].

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

916  [NCBI] & 2322  [NCBI]

P07766 & P36888

ELISA, FACS, Functional assay

Unconjugated

The product can be reconstituted/diluted with sterile PBS or saline.

105.892 kDa

2449199-61-3

Liquid

Colorless to light yellow

[Emirodatamab]

Shipping with dry ice.

Please refer to the lot-specific COA for specific buffer information.

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

• 
  (scFv-heavy-kappa)-(scFv-heavy-lambda)-scFc

• 
  Immobilized CD3 epsilon Protein, Human (HEK293, His, HY-P70506) can bind Emirodatamab. The EC₅₀ for this effect is 26.57 ng/mL.
• 
  Immobilized FLT3 Protein, Human (T227M, HEK293, His, HY-P75183) can bind Emirodatamab. The EC₅₀ for this effect is 11.97 ng/mL.
• 
  Flow cytometric analysis of 1×10⁶ Jurkat cells labelling CD3E (red) with Emirodatamab (HY-P99916). Cells were fixed with 4% paraformaldehyde and permeabilised with 90% methanol. Then stained with the primary antibody at 1/200 dilution for an hour at 4℃. Alexa 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 Isotype Control (HY-P99001, blue) was used as the isotype control, cells without incubation with primary antibody were used as the unlabeled control (black).

• [1]. Obszański P, et al. Molecular-Targeted Therapy of Pediatric Acute Myeloid Leukemia. Molecules. 2022;27(12):3911. Published 2022 Jun 18.  [Content Brief]

  [2]. Morse JW, et al. Antibody therapies for the treatment of acute myeloid leukemia: exploring current and emerging therapeutic targets. Expert Opin Investig Drugs. 2023;32(2):107-125.  [Content Brief]

  [3]. Einsele H, et al. The BiTE (bispecific T-cell engager) platform: Development and future potential of a targeted immuno-oncology therapy across tumor types. Cancer. 2020;126(14):3192-3201.  [Content Brief]

  [4]. Daver N, et al. T-cell-based immunotherapy of acute myeloid leukemia: current concepts and future developments. Leukemia. 2021;35(7):1843-1863.  [Content Brief]

  [5]. Brauchle B, et al. Characterization of a novel FLT3 BiTE molecule for the treatment of acute myeloid leukemia[J]. Molecular Cancer Therapeutics, 2020, 19(9): 1875-1888.