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Marina S. Drutskaya, Maxim A. Nosenko, Ekaterina A. Gorshkova, Vladislav V. Mokhonov, Ruslan V. Zvartsev, Almina I. Polinova, Andrey A. Kruglov, Sergei A. Nedospasov, Effects of myeloid cell-restricted TNF inhibitors in vitro and in vivo, Journal of Leukocyte Biology, Volume 107, Issue 6, June 2020, Pages 933–939, https://doi.org/10.1002/JLB.3AB0120-532R
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Abstract
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.