Bacteroides fragilis-stimulated interleukin-10 contains expanding disease
Cytokines;Chemokines;细胞因子;趋化因子;MSD;Cytokines;Chemokines- J Infect Dis.
- 2011
- 7.759
- 411(4):791-807.
- Human,Mouse,Non-Human Primate
- MSD
- Serum
- 免疫/内分泌
- IL-17A
相关货号
LXMH07-1LXMH09-2LXMH09-4LXMH10-2LXMH10-4LXMH10-5LXMH111-1LXMH14-1LXMH30-1LXMH37-1LXMH40-1LXMH44-1LXMH46-1LXMH54-1LXMH71-1LXMH87-1LXMM09-2LXMM10-2LXMM10-4LXMM14-1LXMM50-1LXMM58-1LXMN09-1LXMN09-3LXMN10-3LXMN12-1LXMN24-2LXMN61-1
Abstract
The differentiation of therapeutic monoclonal antibodies in an increasingly competitive landscape requires optimization of clinical efficacy combined with increased patient convenience. We describe here the generation of MEDI5117, a human anti-interleukin (IL)-6 antibody generated by variable domain engineering, to achieve subpicomolar affinity for IL-6, combined with Fc (fragment crystallizable) engineering to enhance pharmacokinetic half-life. MEDI5117 was shown to be highly potent in disease-relevant cellular assays. The pharmacokinetics of MEDI5117 were evaluated and compared to those of its progenitor, CAT6001, in a single-dose study in cynomolgus monkeys. The antibodies were administered, either subcutaneously or intravenously, as a single dose of 5 mg/kg. The half-life of MEDI5117 was extended by approximately 3-fold, and clearance was reduced by approximately 4-fold when compared to CAT6001. MEDI5117 therefore represents a potential 'next-generation' antibody; future studies are planned to determine the potential for affinity-driven efficacy and/or less frequent administration.
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