Human Anti-IFNAR1 Recombinant Antibody (clone MEDI546) (CAT#: PABL-228)

Recombinant Antagonist Human Antibody (MEDI546) is capable of binding to IFNAR1, expressed in HEK 293 cells. Expressed as the combination of a heavy chain (HC) containing VH from anti-IFNAR1 mAb and CH1-3 region of human IgG1 and a light chain (LC) encoding VL from anti-IFNAR1 mAb and CL of human kappa light chain. Exists as a disulfide linked dimer of the HC and LC hetero-dimer under non-reducing condition.

Specific Inquiry
  • Size:
  • Conjugation:
  • Endotoxin:
  • Purity:
  • Fc Engineering:
  • Published Data
  • Gene Expression
  • Datasheet
  • MSDS
  • COA

Figure 1 Mean (±SD) serum MEDI-546 concentration.

Figure 1 Mean (±SD) serum MEDI-546 concentration.

A. Single IV Administration; B. Multiple IV Administrations. LLOQ, lower limit of quantitation; SD, standard deviation. Mean data below LLOQ are not plotted.

Goldberg, A., Geppert, T., Schiopu, E., Frech, T., Hsu, V., Simms, R. W.,... & Wang, B. (2014). Dose-escalation of human anti-interferon-α receptor monoclonal antibody MEDI-546 in subjects with systemic sclerosis: a phase 1, multicenter, open label study. Arthritis research & therapy,16(1), R57.

Figure 2 Membrane binding of A488-labelled anifrolumab to IFNAR1, and the APC-labelled membrane marker CD11b antibody, on primary human monocytes at 0 and 30min after placing cells under internalisation conditions of 37°C and 5% carbon dioxide (CO2).

Figure 2 Membrane binding of A488-labelled anifrolumab to IFNAR1, and the APC-labelled membrane marker CD11b antibody, on primary human monocytes at 0 and 30min after placing cells under internalisation conditions of 37°C and 5% carbon dioxide (CO2).

Riggs, J. M., Hanna, R. N., Rajan, B., Zerrouki, K., Karnell, J. L., Sagar, D.,... & de los Reyes, M. (2018). Characterisation of anifrolumab, a fully human anti-interferon receptor antagonist antibody for the treatment of systemic lupus erythematosus.Lupus science & medicine, 5(1), e000261.

Figure 3 Anifrolumab inhibits type I interferon (IFN)-induced IFN-stimulated response element (ISRE) signalling.

Figure 3 Anifrolumab inhibits type I interferon (IFN)-induced IFN-stimulated response element (ISRE) signalling.

Type I IFNinduced luciferase activity in HEK293-ISRE reporter cells elicited by (A) recombinant IFN-α2 protein (100 (triangles), 1000 (squares), 10 000 (circles) or 100 000 (diamonds) U/mL); (B and C) CpG-A-stimulated and DNA/IgG–immune complexes (DNAIC)-stimulated pDC supernatant (diluted 1:10 (triangles), 1:100 (squares) or 1:1000 (circles)), with preincubation with anifrolumab (black symbols) or isotype control antibody (white open circles). Type I IFN-induced luciferase activity in pIL5-ISRE reporter cells elicited by sera from patients with SLE with and without preincubation with anifrolumab or isotype control antibody; (D) representative assay with a single serum sample and anifrolumab IC50 of 0.05nM and (E) relative IFN activity of 20 serum samples. Mean IC50 for sera from three patients with SLE was 0.32±0.50nM.

Riggs, J. M., Hanna, R. N., Rajan, B., Zerrouki, K., Karnell, J. L., Sagar, D.,... & de los Reyes, M. (2018). Characterisation of anifrolumab, a fully human anti-interferon receptor antagonist antibody for the treatment of systemic lupus erythematosus.Lupus science & medicine, 5(1), e000261.

Figure 4 Anifrolumab inhibits cytokine production, plasmacytoid dendritic cell (pDC) activation and the type I (interferon gene signature) IFN gene signature.

Figure 4 Anifrolumab inhibits cytokine production, plasmacytoid dendritic cell (pDC) activation and the type I (interferon gene signature) IFN gene signature.

IFN-α production by CpG-A-stimulated and DNA/IgG–immune complexes (DNA-IC)-stimulated (A) peripheral blood mononuclear cells (PBMCs) and (B) pDCs with and without preincubation with anifrolumab or isotype control antibody. Dose–response curve of antibody inhibition of IFN-α from a representative donor stimulated with (A and B, left panel) CpG-A or (A and B, centre panel) DNA-IC and (A and B, right panel) quantification of IFN inhibition in multiple donors at 10µg/mL (67.7 nM) anifrolumab or isotype control antibody. (C, left panel) Induction of the 21-gene IFN gene signature in CpG-A-stimulated PBMCs from three donors. (C, right panel) Inhibition of the 21-gene IFN gene signature in CpG-A-stimulated PBMCs from seven donors with and without preincubation with anifrolumab or isotype control antibody. (D) CD80 activation and CD83 maturation surface marker expression in CpG-A-stimulated pDCs with and without preincubation with 10µg/mL (67.7 nM) anifrolumab or isotype control antibody. (E) TNF-α, interleukin (IL)-6 and IL-8 secretion from CpG-A-stimulated pDCs with and without preincubation with 10 µg/mL (67.7 nM) anifrolumab or isotype control antibody.

Riggs, J. M., Hanna, R. N., Rajan, B., Zerrouki, K., Karnell, J. L., Sagar, D.,... & de los Reyes, M. (2018). Characterisation of anifrolumab, a fully human anti-interferon receptor antagonist antibody for the treatment of systemic lupus erythematosus.Lupus science & medicine, 5(1), e000261.

Figure 5 Anifrolumab suppresses plasmacytoid dendritic cell (pDC)-dependent plasma cell differentiation.

Figure 5 Anifrolumab suppresses plasmacytoid dendritic cell (pDC)-dependent plasma cell differentiation.

(A) Representative flow cytometry plots and quantification of plasma cell (CD19+ CD27highCD38high) differentiation in untreated, interleukin (IL)-21- stimulated (positive control) or CpG-A-stimulated B cell/pDC co-cultures. (B) Representative flow cytometry plot and (C and D) quantification of plasma cell differentiation in CpG-A-stimulated B cell/pDC co-cultures with and without preincubation with anifrolumab or control antibody.

Riggs, J. M., Hanna, R. N., Rajan, B., Zerrouki, K., Karnell, J. L., Sagar, D.,... & de los Reyes, M. (2018). Characterisation of anifrolumab, a fully human anti-interferon receptor antagonist antibody for the treatment of systemic lupus erythematosus.Lupus science & medicine, 5(1), e000261.


Specifications

  • Immunogen
  • Human interferon (alpha, beta and omega) receptor 1
  • Host Species
  • Human
  • Type
  • Human IgG
  • Specificity
  • Human IFNAR1
  • Species Reactivity
  • Human
  • Clone
  • MEDI546
  • Applications
  • WB, ELISA, FuncS

Product Property

  • Purity
  • >95% as determined by SDS-PAGE and HPLC analysis
  • Concentration
  • Please refer to the vial label for the specific concentration.
  • Storage
  • Centrifuge briefly prior to opening vial. Store at +4°C short term (1-2 weeks). Aliquot and store at -20°C long term. Avoid repeated freeze/thaw cycles.

Applications

  • Application Notes
  • The antibody was validated for Immunofluorescence and Inhibition. For details, refer to Published Data.

Target

  • Alternative Names
  • IFNAR1; interferon (alpha; beta and omega) receptor 1; AVP; IFRC; IFNAR; IFNBR; IFN-alpha-REC; interferon alpha/beta receptor 1; CRF2-1; IFN-R-1; IFN-alpha/beta receptor 1; interferon-beta receptor 1; beta-type antiviral protein; alpha-type antiviral protein; type I interferon receptor 1; cytokine receptor class-II member 1; cytokine receptor family 2 member 1; interferon-alpha/beta receptor alpha chain

Product Notes

This is a product of Creative Biolabs' Hi-Affi™ recombinant antibody portfolio, which has several benefits including:

• Increased sensitivity
• Confirmed specificity
• High repeatability
• Excellent batch-to-batch consistency
• Sustainable supply
• Animal-free production

See more details about Hi-Affi™ recombinant antibody benefits.

Downloads

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Humanized Antibody

Neutralizing Antibody

CAT Product Name Application Type
NEUT-976CQ Mouse Anti-Ifnar1 Recombinant Antibody (clone MAR1-5A3) FC, Neut, IP, WB, B Mouse IgG1

Rabbit Monoclonal Antibody

CAT Product Name Application Type
MOR-1740 Rabbit Anti-IFNAR1 Recombinant Antibody (clone DS1740AB) WB, FC, IP Rabbit IgG

ADCC Enhanced Antibody

CAT Product Name Application Type
AFC-TAB-722 Afuco™ Anti-IFNAR ADCC Recombinant Antibody (Anifrolumab), ADCC Enhanced FuncS, IF, Neut, ELISA, FC, IP ADCC enhanced antibody

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