Nanobody-mediated complement activation to kill HIV-infected cells.
HIV-1
bispecific complement engager
complement
immunotherapy
nanobody
Journal
EMBO molecular medicine
ISSN: 1757-4684
Titre abrégé: EMBO Mol Med
Pays: England
ID NLM: 101487380
Informations de publication
Date de publication:
11 04 2023
11 04 2023
Historique:
revised:
02
02
2023
received:
08
06
2022
accepted:
03
02
2023
medline:
12
4
2023
pubmed:
18
2
2023
entrez:
17
2
2023
Statut:
ppublish
Résumé
The complement system which is part of the innate immune response against invading pathogens represents a powerful mechanism for killing of infected cells. Utilizing direct complement recruitment for complement-mediated elimination of HIV-1-infected cells is underexplored. We developed a novel therapeutic modality to direct complement activity to the surface of HIV-1-infected cells. This bispecific complement engager (BiCE) is comprised of a nanobody recruiting the complement-initiating protein C1q, and single-chain variable fragments of broadly neutralizing antibodies (bNAbs) targeting the HIV-1 envelope (Env) protein. Here, we show that two anti-HIV BiCEs targeting the V3 loop and the CD4 binding site, respectively, increase C3 deposition and mediate complement-dependent cytotoxicity (CDC) of HIV-1 Env-expressing Raji cells. Furthermore, anti-HIV BiCEs trigger complement activation on primary CD4 T cells infected with laboratory-adapted HIV-1 strain and facilitates elimination of HIV-1-infected cells over time. In summary, we present a novel approach to direct complement deposition to the surface of HIV-1-infected cells leading to complement-mediated killing of these cells.
Identifiants
pubmed: 36799046
doi: 10.15252/emmm.202216422
pmc: PMC10086584
doi:
Substances chimiques
Antibodies, Neutralizing
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e16422Subventions
Organisme : Danmarks Frie Forskningsfond
ID : 9039-00039B
Organisme : Danmarks Frie Forskningsfond
ID : 1029-00004B
Organisme : Novo Nordisk Fonden
ID : NNF19OC0054577
Informations de copyright
© 2023 The Authors. Published under the terms of the CC BY 4.0 license.
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