Evidence map›Paper›PMID 32287071›Full record

ArticleAIDS (London, England)2020

Enhancing natural killer cell function with gp41-targeting bispecific antibodies to combat HIV infection.

Nitya S Ramadoss, Nancy Q Zhao, Barbra A Richardson, Philip M Grant, Peter S Kim, Catherine A Blish

Open access · greenAbstract read
In one paragraph

Article in AIDS (London, England), 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.

0numbers the graph read from it
0cells of the map it votes in
16citing papers in PubMed
0.8field-weighted citation impact, top 29% 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

16 citing papers in PubMed, 19 citations in OpenAlex.

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  12. Engaging innate immunity in HIV-1 cure strategies.Nature reviews. Immunology · 2022
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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

6 authors at 2 institutions in 1 country.

Nitya S RamadossDepartment of Biochemistry.
Nancy Q ZhaoDepartment of Medicine, Division of Infectious Diseases and Geographic Medicine.
Barbra A RichardsonDepartment of Biostatistics, University of Washington, Seattle, Washington.
Philip M GrantDepartment of Medicine, Division of Infectious Diseases and Geographic Medicine.
Peter S KimDepartment of Biochemistry.
Catherine A BlishDepartment of Medicine, Division of Infectious Diseases and Geographic Medicine.
Stanford University · USUniversity of Washington · US

Funding

Making the HIV-1 gp41 pocket amenable to small-molecule drug discoveryDP1DA043893 · NIDA · STANFORD UNIVERSITY · PI KIM, PETER S · 2017 to 2021
$4.3M
Targeting natural killer cells to HIV in intravenous drug usersDP1DA046089 · NIDA · STANFORD UNIVERSITY · PI BLISH, CATHERINE A · 2018 to 2022
$3.9M
NIDA NIH HHS DP1 DA043893NIDA NIH HHS DP1 DA046089
6 · The paper itself

Abstract

OBJECTIVE(S): The aim of this study was to develop and evaluate the activity of bispecific antibodies (bsAbs) to enhance natural killer (NK) cell antibody-dependent cellular cytotoxicity (ADCC) against HIV-infected cells.

designThese bsAbs are based on patient-derived antibodies targeting the conserved gp41 stump of HIV Env, and also incorporate a high-affinity single chain variable fragment (scFv) targeting the activating receptor CD16 on NK cells. Overall, we expect the bsAbs to provide increased affinity and avidity over their corresponding mAbs, allowing for improved ADCC activity against Env-expressing target cells.

methodsbsAbs and their corresponding mAbs were expressed in 293T cells and purified. The binding of bsAbs and mAbs to their intended targets was determined using Bio-Layer Interferometry, as well as flow cytometry based binding assays on in-vitro infected cells. The ability of these bsAbs to improve NK cell activity against HIV-infected cells was tested using in-vitro co-culture assays, using flow cytometry and calcein release to analyse NK cell degranulation and target cell killing, respectively.

resultsThe bsAbs-bound gp41 with similar affinity to their corresponding mAbs had increased affinity for CD16. The bsAbs also bound to primary CD4 T cells infected in vitro with two different strains of HIV. In addition, the bsAbs induce increased NK cell degranulation and killing of autologous HIV-infected CD4 T cells.

conclusionOn the basis of their in-vitro killing efficacy, bsAbs may provide a promising strategy to improve NK-mediated immune targeting of infected cells during HIV infection.

Indexed as

Antibodies, BispecificAntibody-Dependent Cell CytotoxicityHIV-1HIV AntibodiesHIV Envelope Protein gp41HIV InfectionsHumansKiller Cells, NaturalPeptide FragmentsAntibodies, BispecificHIV AntibodiesHIV Envelope Protein gp41Peptide Fragmentspeptide N36

Identifiers

PMID32287071
PMCPMC7595577
OpenAlexW3015234297

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.