Efizonerimod alfa  (Synonyms: MEDI-6383)

Efizonerimod alfa (MEDI-6383) is a recombinant human OX40L IgG4P Fc fusion protein that assembles into a hexameric structure and exerts potent agonist activity upon binding to OX40. The activity of Efizonerimod alfa is enhanced by Fcγ receptor-mediated aggregation. Efizonerimod alfa binds to OX40 on the surface of activated T cells, induces NF-κB promoter activity in OX40-expressing T cells, and triggers the production of Th1-type cytokines, T cell proliferation, and resistance to regulatory T cell (Treg)-mediated suppression. Efizonerimod alfa enhances the cytolytic activity of tumor-reactive T cells and slows tumor growth in immunodeficient mice. Efizonerimod alfa induces the proliferation of CD4, CD8, and B cells in the peripheral blood of healthy non-human primates. Efizonerimod alfa can be used in the research of advanced solid malignancies and melanoma^[1].

OX40^[1]

Efizonerimod alfa (MEDI-6383) potently binds OX40 on activated human, cynomolgus, and rhesus CD4⁺ T cells with mean apparent K_d values ranging from 1.7 to 24 pM^[1].
Efizonerimod alfa (0.01 pM-1 nM; 45 min) induces dose-dependent NF-κB signaling in human OX40-expressing Jurkat T cells, with activity significantly enhanced by FcγR-mediated clustering via CD32A, CD64, CD32B, or primary tumor-derived CD45⁺ immune cells, but not CD16^[1].
Efizonerimod alfa, containing an IgG4P Fc domain, does not induce NK cell-mediated ADCC of OX40-expressing CD4⁺ T cells or bind complement component C1q^[1].
Efizonerimod alfa (0.01 pM-10 nM; 72 h) induces concentration-dependent cytokine release (Th1 and Th2 type) and CD4⁺ T-cell proliferation in activated primary human CD3⁺ T cells in a TCR-dependent manner, and upregulates activation markers on both CD4⁺ and CD8⁺ T cells^[1].
Efizonerimod alfa induces concentration-dependent proliferation of activated primary human CD4⁺ T cells when clustered by CD32A-expressing HEK293 cells in a TCR-dependent manner^[1].
Efizonerimod alfa (0.076-5.0 nM; 5 d) reverses nTreg-mediated suppression of primary human CD4⁺ effector T cell proliferation and induces concentration-dependent proliferation of primary human CD4⁺ nTregs, both in monoculture and coculture with Teff cells^[1].

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

Efizonerimod alfa (MEDI-6383) (0.1-3 mg/kg; 2 times per week; 2 weeks) induces statistically significant, T-cell-dependent tumor growth inhibition in NOD/SCID mice bearing human A375 melanoma/human T-cell admixtures across doses of 0.1 to 3 mg/kg^[1].
Efizonerimod alfa (1 mg/kg; i.v.; every other day; 3 doses) induces robust proliferation of central and effector memory CD4 and CD8 T cells, upregulates T-cell activation markers, and stimulates B-cell proliferation in healthy rhesus macaques^[1].

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

ELISA, FACS, Functional assay

Unconjugated

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

273.72 kDa

1635395-27-5

Liquid

Colorless to light yellow

[Efizonerimod alfa]

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.

• 
  [IGHG4 Fc (Fragment constant)– [TRAF2 (TNF receptor associated factor 2, TRAP3, RNF117)-TNFSF4 (tumor necrosis factor (TNF)superfamily member 4, OX40 ligand, OX-40L, TAX transcriptionally-activated glycoprotein 1, TXGP1, gp34, CD252)]2]3 (hexamer)

• [1]. Oberst MD, et al. Potent Immune Modulation by MEDI6383, an Engineered Human OX40 Ligand IgG4P Fc Fusion Protein. Mol Cancer Ther. 2018;17(5):1024-1038.  [Content Brief]