Evidence map›Paper›PMID 36799046›Full record

ArticleEMBO molecular medicine2023

Nanobody-mediated complement activation to kill HIV-infected cells.

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

Open access · goldAbstract read
In one paragraph

Article in EMBO molecular medicine, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.

0numbers the graph read from it
0cells of the map it votes in
8citing papers in PubMed
2.8field-weighted citation impact, top 10% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

8 citing papers in PubMed, 13 citations in OpenAlex.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

9 authors at 1 institution in 1 country.

Maria Lange PedersenDepartment of Clinical Medicine, Aarhus University, Aarhus, Denmark.ORCID 0000-0003-4338-2507
Dennis Vestergaard PedersenDepartment of Molecular Biology and Genetics, Aarhus University, Aarhus, Denmark.ORCID 0000-0003-1058-2377
Mikael Becher Lykkegaard WinklerDepartment of Molecular Biology and Genetics, Aarhus University, Aarhus, Denmark.ORCID 0000-0003-0675-7824
Heidi Gytz OlesenDepartment of Molecular Biology and Genetics, Aarhus University, Aarhus, Denmark.ORCID 0000-0003-4870-9214
Ole Schmeltz SøgaardDepartment of Clinical Medicine, Aarhus University, Aarhus, Denmark.ORCID 0000-0001-9107-2023
Lars ØstergaardDepartment of Clinical Medicine, Aarhus University, Aarhus, Denmark.ORCID 0000-0002-7619-605X
Nick Stub LaursenDepartment of Biomedicine, Aarhus University, Aarhus, Denmark.ORCID 0000-0002-7512-2649
Anna Halling Folkmar RahimicDepartment of Clinical Medicine, Aarhus University, Aarhus, Denmark.ORCID 0000-0003-0681-3611
Martin TolstrupDepartment of Clinical Medicine, Aarhus University, Aarhus, Denmark.ORCID 0000-0001-7020-5173
Aarhus University · DK

Funding

Danmarks Frie Forskningsfond 1029-00004BDanmarks Frie Forskningsfond 9039-00039BNovo Nordisk Fonden NNF19OC0054577
6 · The paper itself

Abstract

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.

Indexed as

HIV-1HIV InfectionsAntibodies, NeutralizingCD4-Positive T-LymphocytesComplement ActivationHumansAntibodies, Neutralizingbispecific complement engagercomplementHIV-1immunotherapynanobody

Identifiers

PMID36799046
PMCPMC10086584
OpenAlexW4321163523

What OpenQuestion holds

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Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.