sifalimumab   Click here for help

GtoPdb Ligand ID: 8257

Synonyms: MDX-1103 | MEDI-545 | MEDI545
Immunopharmacology Ligand
Compound class: Antibody
Comment: Sifalimumab is a monoclonal antibody targeting interferon α1 (IFNA1), that was developed by the MedImmune subsidiary of AstraZeneca as a treatment for systemic lupus erythematosus (SLE). Development of sifalimumab was terminated and MedImmune concentrated on their alternative anti-IFNα agent anifrolumab.
Peptide sequence and structural information for this antibody are available from its IMGT/mAb-db record. Sequence BLAST using the heavy and light chain variable regions of sifalimumab provides 100% matches to sequences patented with application US7741449 [12]. The sequence matches identify sifalimumab as clone 13H5 in the patent.
References
1. Batteux F, Palmer P, Daëron M, Weill B, Lebon P. (1999)
FCgammaRII (CD32)-dependent induction of interferon-alpha by serum from patients with lupus erythematosus.
Eur Cytokine Netw, 10 (4): 509-14. [PMID:10586117]
2. Blanco P, Palucka AK, Gill M, Pascual V, Banchereau J. (2001)
Induction of dendritic cell differentiation by IFN-alpha in systemic lupus erythematosus.
Science, 294 (5546): 1540-3. [PMID:11711679]
3. Foulis AK, Farquharson MA, Meager A. (1987)
Immunoreactive alpha-interferon in insulin-secreting beta cells in type 1 diabetes mellitus.
Lancet, 2 (8573): 1423-7. [PMID:2891993]
4. Greth W, Robbie GJ, Brohawn P, Hultquist M, Yao B. (2017)
Targeting the interferon pathway with sifalimumab for the treatment of systemic lupus erythematosus.
Immunotherapy, 9 (1): 57-70. [PMID:28000522]
5. Hooks JJ, Jordan GW, Cupps T, Moutsopoulos HM, Fauci AS, Notkins AL. (1982)
Multiple interferons in the circulation of patients with systemic lupus erythematosus and vasculitis.
Arthritis Rheum, 25 (4): 396-400. [PMID:6176247]
6. Khamashta M, Merrill JT, Werth VP, Furie R, Kalunian K, Illei GG, Drappa J, Wang L, Greth W, CD1067 study investigators. (2016)
Sifalimumab, an anti-interferon-α monoclonal antibody, in moderate to severe systemic lupus erythematosus: a randomised, double-blind, placebo-controlled study.
Ann Rheum Dis, 75 (11): 1909-1916. [PMID:27009916]
7. Luft T, Luetjens P, Hochrein H, Toy T, Masterman KA, Rizkalla M, Maliszewski C, Shortman K, Cebon J, Maraskovsky E. (2002)
IFN-alpha enhances CD40 ligand-mediated activation of immature monocyte-derived dendritic cells.
Int Immunol, 14 (4): 367-80. [PMID:11934873]
8. Luft T, Pang KC, Thomas E, Hertzog P, Hart DN, Trapani J, Cebon J. (1998)
Type I IFNs enhance the terminal differentiation of dendritic cells.
J Immunol, 161 (4): 1947-53. [PMID:9712065]
9. Paquette RL, Hsu NC, Kiertscher SM, Park AN, Tran L, Roth MD, Glaspy JA. (1998)
Interferon-alpha and granulocyte-macrophage colony-stimulating factor differentiate peripheral blood monocytes into potent antigen-presenting cells.
J Leukoc Biol, 64 (3): 358-67. [PMID:9738663]
10. Radvanyi LG, Banerjee A, Weir M, Messner H. (1999)
Low levels of interferon-alpha induce CD86 (B7.2) expression and accelerates dendritic cell maturation from human peripheral blood mononuclear cells.
Scand J Immunol, 50 (5): 499-509. [PMID:10564553]
11. Santini SM, Lapenta C, Logozzi M, Parlato S, Spada M, Di Pucchio T, Belardelli F. (2000)
Type I interferon as a powerful adjuvant for monocyte-derived dendritic cell development and activity in vitro and in Hu-PBL-SCID mice.
J Exp Med, 191 (10): 1777-88. [PMID:10811870]
12. Witte A, Williams D, Cardarelli JM, King D, Passmore D. (2010)
Anti-interferon Alpha Antibodies.
Patent number: US7741449. Assignee: Medarex, Inc.. Priority date: 10/12/2003. Publication date: 22/06/2010.
13. Ytterberg SR, Schnitzer TJ. (1982)
Serum interferon levels in patients with systemic lupus erythematosus.
Arthritis Rheum, 25 (4): 401-6. [PMID:6176248]