Cusatuzumab  (Synonyms: ARGX-110)

Cusatuzumab (ARGX-110) is a selective competitive blocker targeting CD70 (with an equilibrium dissociation constant of 17 pM for binding to human CD70). Cusatuzumab also possesses enhanced antibody-dependent cell-mediated cytotoxicity (ADCC) activity. It is a humanized IgG1 monoclonal antibody, artificially synthesized through humanization and genetic engineering modifications (CH2 region mutation to enhance effector function). Cusatuzumab has a dual mechanism of action: firstly, it competitively blocks the interaction between CD70 and CD27, inhibiting the CD27-NF-κB signaling pathway, reducing regulatory T cell (Treg) activation and tumor cell proliferation; secondly, by enhancing binding to FcγRIIIa, it mediates ADCC and antibody-dependent cellular phagocytosis (ADCP), directly lysing CD70-positive tumor cells. Cusatuzumab can efficiently eliminate leukemia stem cells (LSCs), induce tumor cell differentiation and apoptosis, restore immune surveillance, and target CD70-positive tumors. Cusatuzumab is used in the study of acute myeloid leukemia (AML)^[1][2].

Human IgG1 lambda2

Human IgG1 lambda2, Isotype Control

Human

TNFSF7/CD27L/CD70

Cusatuzumab (3-100 nM) specifically binds to human CD70 with an equilibrium dissociation constant of 17 pM, and does not bind to CD70-negative cells (SUP-T1, untransfected HEK293). Its binding affinity to FcγRIIIa is 70 times higher than the fucosylated version^[1].
Cusatuzumab (0.01-1 μg/mL; 2 h) induces antibody-dependent cell-mediated cytotoxicity (ADCC), with a 20-fold higher lysis efficiency against 786-O cells compared to the fucosylated version^[1].
Cusatuzumab (0.001-10 μg/mL; 2 h) does not affect complement-dependent cytotoxicity (CDC), and its CDC activity against U266 cells is comparable to the fucosylated version^[1].
Cusatuzumab retains antibody-dependent cellular phagocytosis (ADCP) activity and can mediate the phagocytosis of 786-O cells by monocyte-derived macrophages^[1].
Cusatuzumab (5 μg/mL; 2 days) blocks the proliferation of regulatory T cells (Tregs) induced by CD70-positive tumor cells (Raji, SU-DHL-6, U266) and reduces the level of soluble CD27 (sCD27) in the supernatant^[1].
Cusatuzumab (10 μg/mL; 72 h) in combination with NK cells significantly reduces acute myeloid leukemia stem cell (LSC) colony formation, induces the expression of differentiation genes such as CEBPA and SPI1, and synergistically kills LSCs and leukemia blast cells in combination with Decitabine (HY-A0004), promoting apoptosis^[2].

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

The fucosylated version of Cusatuzumab, 41D12 (0.1 mg/kg and above; i.p.; twice weekly; 5 doses in total), significantly prolongs survival time in a SCID mouse Burkitt lymphoma Raji xenograft model, and serum sCD27 levels are higher in tumor-bearing mice than in tumor-free mice^[1].
Cusatuzumab (1 mg/kg, 3 mg/kg, 10 mg/kg; i.v.; single dose) shows peak plasma concentrations (Cmax) of 50 μg/mL, 151 μg/mL, and 504 μg/mL, respectively, in a normal female cynomolgus monkey model, with a half-life of approximately 12 days and a clearance rate of 0.009 L/day^[1].
Cusatuzumab (10 mg/kg; i.p.; 3 doses in total; administered 5-12 weeks after transplantation) reduces the number of leukemia cells and leukemia stem cells (LSCs) in the bone marrow of a NOD/SCID/γc^-/^- (NSG) mouse acute myeloid leukemia (AML) patient-derived xenograft (PDX) model. When combined with Decitabine (HY-A0004) (1.5 mg/kg/day for 5 consecutive days), it synergistically reduces LSC frequency and lowered serum sCD27 levels^[2].
Cusatuzumab (10 mg/kg; i.p.; 3 doses in total; administered 43 days after transplantation) in an NSG mouse AML PDX model, when combined with NK cells, significantly reduces leukemia cell engraftment and LSC numbers in the bone marrow and spleen, and reduced AML colony formation compared to using Cusatuzumab or NK cells alone^[2].

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

970  [NCBI]

P32970

ELISA, FACS, Functional assay

Unconjugated

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

144.36 kDa

1864871-20-4

Liquid

Colorless to light yellow

[Cusatuzumab]

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.

• 
  Human IgG1 lambda2

• 
  Flow Cytometry analysis of Raji cells labelling TNFSF7/CD27L/CD70 (red) with Cusatuzumab (anti-TNFSF7/CD27L/CD70) (HY-P99014). Goat Anti-Human IgG (Alexa Fluor 488) (HY-P83776) at a dilution of 1/1000 was used as the secondary antibody. Blue-Human IgG1 lambda2 (HY-P990096). Black-Unlabelled control, cells without incubation with primary antibody.

• [1]. Silence K, et al. ARGX-110, a highly potent antibody targeting CD70, eliminates tumors via both enhanced ADCC and immune checkpoint blockade. MAbs. 2014 Mar-Apr;6(2):523-32.  [Content Brief]

  [2]. Riether C, et al. Targeting CD70 with cusatuzumab eliminates acute myeloid leukemia stem cells in patients treated with hypomethylating agents. Nat Med. 2020 Sep;26(9):1459-1467.  [Content Brief]