NGM-438 

NGM-438 is a humanized monoclonal antibody antagonist of LAIR1, with a K_a of 0.26 nM for human LAIR1 and 4.28 nM for cynomolgus monkey LAIR1. NGM-438 blocks the binding of LAIR1 to its Collagen ligand and antagonizes the Collagen-induced LAIR1 signaling pathway. NGM-438 reverses FcγR signaling inhibition in myeloid cells, induces dendritic cells to secrete TNFα, promotes T cell proliferation, and triggers myeloid inflammation and allogeneic T cell responses. NGM-438 sensitizes refractory mouse lung cancer to PD-1 blockade, increases the content of intratumoral CD8⁺ T cells and the expression of inflammatory genes. NGM-438 is applicable to research related to solid tumors, refractory solid tumors and non-small cell lung cancer^[1][2].

Human IgG1 kappa

Human IgG1 kappa, Isotype Control

Human

LAIR-1

NGM-438 exhibits an IC₅₀ of 3.41 nM and 3.05 nM, respectively, in the human and cynomolgus monkey LAIR1-Fc: type 1 collagen blocking enzyme-linked immunosorbent assay, and an EC₅₀ of 0.38 nM and 13.7 nM, respectively, in the human and cynomolgus monkey immune cell binding assay^[1].
NGM-438 binds to recombinant human and cynomolgus monkey LAIR1 with high affinity, with K_d values of 0.26 nM and 4.28 nM, respectively^[2].
NGM-438 (overnight treatment) potently and dose-dependently blocks the binding of LAIR1 to Collagen (HY-NP003), and inhibits Collagen-induced GFP expression in LAIR1-GFP reporter cells exposed to various collagen substrates^[2].
NGM-438 (for 2 days) abrogates the inhibitory effect of Collagen on myeloid inflammation, induces human monocyte-derived dendritic cells (moDCs) to secrete CCL3, CCL4 and IL1RN in a dose-dependent manner, and reprograms the expression of immunosuppressive SAM genes to an inflammatory phenotype^[2].
NGM-438 (overnight treatment) reverses the inhibitory effect of Collagen on FcR-driven myeloid inflammation, and induces dose-dependent TNFα secretion by human monocyte-derived dendritic cells (moDCs)^[2].
Combination of NGM-438 (administered for 4-5 days) with anti-PD-1 reverses Collagen-mediated T cell proliferation inhibition and promotes the secretion of proinflammatory cytokines in human allogeneic MLR assays^[2].

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

Combination of NGM-438 (10 mg/kg; i.p.; twice weekly) with anti-PD-1 significantly reduces primary and metastatic tumor burdens in refractory Kras/p53-mutant NSCLC models, leading to decreased number and reduced volume of lung tumors. This effect correlates with enhanced intratumoral CD8⁺ T cell activity and pro-inflammatory gene expression, and reverses immunosuppression^[2].

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

3903  [NCBI]

Q6GTX8

ELISA, FACS, Functional assay

Unconjugated

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

144.92 kDa

Liquid

Colorless to light yellow

N/A

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.

• 
  Immobilized Human LAIR1/CD305 Protein,Fc Tag can bind NGM-438. The EC₅₀ for this effect is 66.71 ng/mL.
• 
  Flow Cytometry analysis of THP-1 cells labelling LAIR-1 (red) with NGM-438 (HY-P991193). Cells were fixed with 4% paraformaldehyde and permeabilised with 90% methanol. Then cells were 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]. Sisi He, et al. Preclinical Development of NGM438, a Novel Anti-LAIR1 Antagonist
  Monoclonal Antibody for the Treatment of Collagen-Rich Solid Tumors.

  [2]. Rodriguez BL, et al. Antitumor Activity of a Novel LAIR1 Antagonist in Combination with Anti-PD1 to Treat Collagen-Rich Solid Tumors. Mol Cancer Ther. 2024 Aug 1;23(8):1144-1158.  [Content Brief]