AUTHOR=Nosenko Maxim A. , Atretkhany Kamar-Sulu N. , Mokhonov Vladislav V. , Efimov Grigory A. , Kruglov Andrey A. , Tillib Sergei V. , Drutskaya Marina S. , Nedospasov Sergei A. 

TITLE=VHH-Based Bispecific Antibodies Targeting Cytokine Production

JOURNAL=Frontiers in Immunology

VOLUME=8

YEAR=2017

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2017.01073

DOI=10.3389/fimmu.2017.01073

ISSN=1664-3224

ABSTRACT=<p>Proinflammatory cytokines, such as TNF, IL-6, and IL-1, play pathogenic roles in multiple diseases and are attractive targets for biologic drugs. Because proinflammatory cytokines possess non-redundant protective and immunoregulatory functions, their systemic neutralization carries the potential for unwanted side effects. Therefore, next-generation anti-cytokine therapies would seek to selectively neutralize pathogenic cytokine signaling, leaving normal function intact. Fortunately, the biology of proinflammatory cytokines provides several such opportunities. Here, we discuss various applications of bispecific antibodies targeting cytokines with specific focus on selective TNF neutralization targeted directly to the surface of specific populations of monocytes and macrophages. These bispecific antibodies combine an anti-TNF V<sub>H</sub>H with V<sub>H</sub>Hs or scFvs directed against abundant surface molecules on myeloid cells and serve to limit the bioavailability of TNF produced by these cells. Such reagents may become prototypes of a novel class of anti-cytokine biologics.</p>