Properties of Fluorescent Far-Red Anti-TNF Nanobodies

Upregulation of the expression of tumor necrosis factor (TNF-α, TNF) has a significant role in the development of autoimmune diseases. The fluorescent antibodies binding TNF may be used for personalized therapy of TNF-dependent diseases as a tool to predict the response to anti-TNF treatmen...

Full description

Bibliographic Details
Main Authors: Ekaterina N. Gorshkova, Grigory A. Efimov, Ksenia D. Ermakova, Ekaterina A. Vasilenko, Diana V. Yuzhakova, Marina V. Shirmanova, Vladislav V. Mokhonov, Sergei V. Tillib, Sergei A. Nedospasov, Irina V. Astrakhantseva
Format: Article
Language:English
Published: MDPI AG 2018-12-01
Series:Antibodies
Subjects:
Online Access:https://www.mdpi.com/2073-4468/7/4/43
_version_ 1818173951076990976
author Ekaterina N. Gorshkova
Grigory A. Efimov
Ksenia D. Ermakova
Ekaterina A. Vasilenko
Diana V. Yuzhakova
Marina V. Shirmanova
Vladislav V. Mokhonov
Sergei V. Tillib
Sergei A. Nedospasov
Irina V. Astrakhantseva
author_facet Ekaterina N. Gorshkova
Grigory A. Efimov
Ksenia D. Ermakova
Ekaterina A. Vasilenko
Diana V. Yuzhakova
Marina V. Shirmanova
Vladislav V. Mokhonov
Sergei V. Tillib
Sergei A. Nedospasov
Irina V. Astrakhantseva
author_sort Ekaterina N. Gorshkova
collection DOAJ
description Upregulation of the expression of tumor necrosis factor (TNF-α, TNF) has a significant role in the development of autoimmune diseases. The fluorescent antibodies binding TNF may be used for personalized therapy of TNF-dependent diseases as a tool to predict the response to anti-TNF treatment. We generated recombinant fluorescent proteins consisting of the anti-TNF module based on the variable heavy chain (VHH) of camelid antibodies fused with the far-red fluorescent protein Katushka (Kat). Two types of anti-TNF VHH were developed: one (BTN-Kat) that was bound both human or mouse TNF, but did not neutralize their activity, and a second (ITN-Kat) that was binding and neutralizing human TNF. BTN-Kat does not interfere with TNF biological functions and can be used for whole-body imaging. ITN-Kat can be evaluated in humanized mice or in cells isolated from humanized mice. It is able to block human TNF (hTNF) activities both in vitro and in vivo and may be considered as a prototype of a theranostic agent for autoimmune diseases.
first_indexed 2024-12-11T19:36:39Z
format Article
id doaj.art-c932b57ac3ec4c239f2f52d04e923ce1
institution Directory Open Access Journal
issn 2073-4468
language English
last_indexed 2024-12-11T19:36:39Z
publishDate 2018-12-01
publisher MDPI AG
record_format Article
series Antibodies
spelling doaj.art-c932b57ac3ec4c239f2f52d04e923ce12022-12-22T00:53:09ZengMDPI AGAntibodies2073-44682018-12-01744310.3390/antib7040043antib7040043Properties of Fluorescent Far-Red Anti-TNF NanobodiesEkaterina N. Gorshkova0Grigory A. Efimov1Ksenia D. Ermakova2Ekaterina A. Vasilenko3Diana V. Yuzhakova4Marina V. Shirmanova5Vladislav V. Mokhonov6Sergei V. Tillib7Sergei A. Nedospasov8Irina V. Astrakhantseva9Center of Molecular Biology and Biomedicine, Institute of Biology and Biomedicine, Lobachevsky State University, Nizhniy Novgorod 603950, RussiaLaboratory of Transplantation Immunology, National Research Center for Hematology, Moscow 125167, RussiaCenter of Molecular Biology and Biomedicine, Institute of Biology and Biomedicine, Lobachevsky State University, Nizhniy Novgorod 603950, RussiaCenter of Molecular Biology and Biomedicine, Institute of Biology and Biomedicine, Lobachevsky State University, Nizhniy Novgorod 603950, RussiaInstitute of Biomedical Technologies, Nizhny Novgorod State Medical Academy, Nizhniy Novgorod 603005, RussiaInstitute of Biomedical Technologies, Nizhny Novgorod State Medical Academy, Nizhniy Novgorod 603005, RussiaCenter of Molecular Biology and Biomedicine, Institute of Biology and Biomedicine, Lobachevsky State University, Nizhniy Novgorod 603950, RussiaLomonosov Moscow State University, Moscow 119991, RussiaCenter of Molecular Biology and Biomedicine, Institute of Biology and Biomedicine, Lobachevsky State University, Nizhniy Novgorod 603950, RussiaCenter of Molecular Biology and Biomedicine, Institute of Biology and Biomedicine, Lobachevsky State University, Nizhniy Novgorod 603950, RussiaUpregulation of the expression of tumor necrosis factor (TNF-α, TNF) has a significant role in the development of autoimmune diseases. The fluorescent antibodies binding TNF may be used for personalized therapy of TNF-dependent diseases as a tool to predict the response to anti-TNF treatment. We generated recombinant fluorescent proteins consisting of the anti-TNF module based on the variable heavy chain (VHH) of camelid antibodies fused with the far-red fluorescent protein Katushka (Kat). Two types of anti-TNF VHH were developed: one (BTN-Kat) that was bound both human or mouse TNF, but did not neutralize their activity, and a second (ITN-Kat) that was binding and neutralizing human TNF. BTN-Kat does not interfere with TNF biological functions and can be used for whole-body imaging. ITN-Kat can be evaluated in humanized mice or in cells isolated from humanized mice. It is able to block human TNF (hTNF) activities both in vitro and in vivo and may be considered as a prototype of a theranostic agent for autoimmune diseases.https://www.mdpi.com/2073-4468/7/4/43TNFfluorescentnanobodiessensoranti-cytokine therapyautoimmune disease
spellingShingle Ekaterina N. Gorshkova
Grigory A. Efimov
Ksenia D. Ermakova
Ekaterina A. Vasilenko
Diana V. Yuzhakova
Marina V. Shirmanova
Vladislav V. Mokhonov
Sergei V. Tillib
Sergei A. Nedospasov
Irina V. Astrakhantseva
Properties of Fluorescent Far-Red Anti-TNF Nanobodies
Antibodies
TNF
fluorescent
nanobodies
sensor
anti-cytokine therapy
autoimmune disease
title Properties of Fluorescent Far-Red Anti-TNF Nanobodies
title_full Properties of Fluorescent Far-Red Anti-TNF Nanobodies
title_fullStr Properties of Fluorescent Far-Red Anti-TNF Nanobodies
title_full_unstemmed Properties of Fluorescent Far-Red Anti-TNF Nanobodies
title_short Properties of Fluorescent Far-Red Anti-TNF Nanobodies
title_sort properties of fluorescent far red anti tnf nanobodies
topic TNF
fluorescent
nanobodies
sensor
anti-cytokine therapy
autoimmune disease
url https://www.mdpi.com/2073-4468/7/4/43
work_keys_str_mv AT ekaterinangorshkova propertiesoffluorescentfarredantitnfnanobodies
AT grigoryaefimov propertiesoffluorescentfarredantitnfnanobodies
AT kseniadermakova propertiesoffluorescentfarredantitnfnanobodies
AT ekaterinaavasilenko propertiesoffluorescentfarredantitnfnanobodies
AT dianavyuzhakova propertiesoffluorescentfarredantitnfnanobodies
AT marinavshirmanova propertiesoffluorescentfarredantitnfnanobodies
AT vladislavvmokhonov propertiesoffluorescentfarredantitnfnanobodies
AT sergeivtillib propertiesoffluorescentfarredantitnfnanobodies
AT sergeianedospasov propertiesoffluorescentfarredantitnfnanobodies
AT irinavastrakhantseva propertiesoffluorescentfarredantitnfnanobodies