Nanobody‐mediated complement activation to kill HIV ‐infected cells

Autor: Maria Lange Pedersen, Dennis Vestergaard Pedersen, Mikael Becher Lykkegaard Winkler, Heidi Gytz Olesen, Ole Schmeltz Søgaard, Lars Østergaard, Nick Stub Laursen, Anna Halling Folkmar Rahimic, Martin Tolstrup
Rok vydání: 2023
Předmět:
Zdroj: Pedersen, M L, Pedersen, D V, Winkler, M B L, Olesen, H G, Søgaard, O S, Østergaard, L, Laursen, N S, Rahimic, A H F & Tolstrup, M 2023, ' Nanobody-mediated complement activation to kill HIV-infected cells ', EMBO Molecular Medicine, vol. 15, no. 4, e16422 . https://doi.org/10.15252/emmm.202216422
ISSN: 1757-4684
1757-4676
Popis: 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.
Databáze: OpenAIRE
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