Bispecific Mini-Antibody with an Anti-CD14 Module Effectively Controls Bioavailability of the Human Tumor Necrosis Factor Produced by Human Monocytes

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Ivan Y. Konev¹, Kirill V. Korneev², Stanislav V. Kozlovsky³, Dmitry V. Dianov⁴, Anna M. Litvinova^1,2, Nina I. Drize⁴, Stanislav A. Rybtsov¹, Ekaterina O. Gubernatorova², Fedor A. Sysonov^2,5, Marina S. Drutskaya^1,2,5,a*, and Sergei A. Nedospasov^1,2,5,b*

¹Division of Immunobiology and Biomedicine, Sirius University of Science and Technology, 354349 Sochi, Krasnodar Region, Russia

²Laboratory of Molecular Mechanisms of Immunity, Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, 119991 Moscow, Russia

³HyTest Ltd, 117105 Moscow, Russia

⁴National Medical Research Center of Hematology, Ministry of Health of the Russian Federation, 125167 Moscow, Russia

⁵Faculty of Biology, Lomonosov Moscow State University, 119991 Moscow, Russia

^* To whom correspondence should be addressed.

Received: December 15, 2025; Revised: March 15, 2026; Accepted: March 16, 2026

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Systemic blockade of proinflammatory cytokines such as IL-1, TNF, and IL-6 using therapeutic antibodies has proven effective in treating a wide range of autoimmune and other chronic inflammatory diseases. However, such blockade also suppresses non-redundant protective and homeostatic functions of cytokines, leading to a number of undesirable side effects. In this study, a novel bispecific mini-antibody featuring modules targeting human TNF and CD14 demonstrated efficacy in controlling TNF secretion from human peripheral blood monocytes. Administration of this antibody protected humanized TNF mice from lethal hepatotoxicity induced by a combination of LPS and D-galactosamine.

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KEY WORDS: cytokine blockers, bispecific antibody, TNF, myeloid cells

DOI: 10.1134/S0006297925604356

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