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Effects of myeloid cell‐restricted TNF inhibitors in vitro and in vivo
Author(s) -
Drutskaya Marina S.,
Nosenko Maxim A.,
Gorshkova Ekaterina A.,
Mokhonov Vladislav V.,
Zvartsev Ruslan V.,
Polinova Almina I.,
Kruglov Andrey A.,
Nedospasov Sergei A.
Publication year - 2020
Publication title -
journal of leukocyte biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.819
H-Index - 191
eISSN - 1938-3673
pISSN - 0741-5400
DOI - 10.1002/jlb.3ab0120-532r
Subject(s) - in vivo , tumor necrosis factor alpha , immunology , biology , antibody , arthritis , myeloid , in vitro , pharmacology , secretion , cancer research , biochemistry , microbiology and biotechnology
Systemic TNF neutralization can be used as a therapy for several autoimmune diseases. To evaluate the effects of cell type‐restricted TNF blockade, we previously generated bispecific antibodies that can limit TNF secretion by myeloid cells (myeloid cell‐specific TNF inhibitors or MYSTIs). In this study several such variable domain (VH) of a camelid heavy‐chain only antibody‐based TNF inhibitors were compared in relevant experimental models, both in vitro and in vivo. Pretreatment with MYSTI‐2, containing the anti‐F4/80 module, can restrict the release of human TNF (hTNF) from LPS‐activated bone marrow‐derived macrophage (BMDM) cultures of humanized TNF knock‐in (mice; hTNFKI) more effectively than MYSTI‐3, containing the anti‐CD11b module. MYSTI‐2 was also superior to MYSTI‐3 in providing in vivo protection in acute toxicity model. Finally, MYSTI‐2 was at least as effective as Infliximab in preventing collagen antibody‐induced arthritis. This study demonstrates that a 33 kDa bispecific mini‐antibody that specifically restricts TNF secretion by macrophages is efficient for amelioration of experimental arthritis.