Cell-type-restricted anti-cytokine therapy: TNF inhibition from one pathogenic sourceстатья
Статья опубликована в высокорейтинговом журнале
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Статья опубликована в журнале из списка Web of Science и/или Scopus
Дата последнего поиска статьи во внешних источниках: 24 мая 2016 г.
Аннотация:Overexpression of TNF contributes to pathogenesis of multiple
autoimmune diseases, accounting for a remarkable success of antiTNF
therapy. TNF is produced by a variety of cell types, and it can play
either a beneficial or a deleterious role. In particular, in autoimmunity
pathogenic TNF may be derived from restricted cellular sources. In this
study we evaluated the feasibility of cell-type–restricted TNF inhibition
in vivo. To this end, we engineered MYSTI (Myeloid-Specific TNF
Inhibitor)—a recombinant bispecific antibody that binds to the F4/80
surface molecule on myeloid cells and to human TNF (hTNF). In macrophage
cultures derived from TNF humanized mice MYSTI could capture
the secreted hTNF, limiting its bioavailability. Additionally, as
evaluated in TNF humanized mice, MYSTI was superior to an otherwise
analogous systemic TNF inhibitor in protecting mice from lethal
LPS/D-Galactosamine–induced hepatotoxicity. Our results suggest a
novel and more specific approach to inhibiting TNF in pathologies
primarily driven by macrophage-derived TNF.