Evidence map›Paper›PMID 33846531›Full record

ArticleCommunications biology2021

A deimmunized and pharmacologically optimized Toll-like receptor 5 agonist for therapeutic applications.

Vadim Mett, Oleg V Kurnasov, Ivan A Bespalov, Ivan Molodtsov, Craig M Brackett, Lyudmila G Burdelya, Andrei A Purmal, Anatoli S Gleiberman, Ilia A Toshkov, Catherine A Burkhart and 4 more

Open access · goldAbstract read
In one paragraph

Article in Communications biology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.

0numbers the graph read from it
0cells of the map it votes in
7citing papers in PubMed
1.6field-weighted citation impact, top 17% 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

7 citing papers in PubMed, 31 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

14 authors at 4 institutions in 2 countries.

Vadim MettBuffalo BioLabs, LLC, Buffalo, NY, USA.
Oleg V KurnasovSanford Burnham Prebys Medical Discovery Institute, La Jolla, CA, USA.
Ivan A BespalovGenome Protection, Inc., Buffalo, NY, USA.
Ivan MolodtsovGamaleya Research Center of Epidemiology and Microbiology, Moscow, Russia.
Craig M BrackettRoswell Park Comprehensive Cancer Center, Buffalo, NY, USA.
Lyudmila G BurdelyaRoswell Park Comprehensive Cancer Center, Buffalo, NY, USA.
Andrei A PurmalGenome Protection, Inc., Buffalo, NY, USA.
Anatoli S GleibermanGenome Protection, Inc., Buffalo, NY, USA.
Ilia A ToshkovGenome Protection, Inc., Buffalo, NY, USA.
Catherine A BurkhartBuffalo BioLabs, LLC, Buffalo, NY, USA.
Yakov N KoganGenome Protection, Inc., Buffalo, NY, USA.
Ekaterina L AndrianovaGenome Protection, Inc., Buffalo, NY, USA.
Andrei V GudkovGenome Protection, Inc., Buffalo, NY, USA. andrei.gudkov@roswellpark.org.ORCID 0000-0003-2548-0154
Andrei L OstermanSanford Burnham Prebys Medical Discovery Institute, La Jolla, CA, USA.
Roswell Park Comprehensive Cancer Center · USBuffalo BioLabs · USSanford Burnham Prebys Medical Discovery Institute · USGamalei Institute of Epidemiology and Microbiology · RU

Funding

Two-Spirit Films in Indigenous Cancer HealthP30CA016056 · NCI · ROSWELL PARK CANCER INSTITUTE CORP · PI Dean G. Tang · 1985 to 2026
$116.6M
NCI NIH HHS P30 CA016056
6 · The paper itself

Abstract

The Toll-like receptor 5 (TLR5) agonist entolimod, a derivative of Salmonella flagellin, has therapeutic potential for several indications including radioprotection and cancer immunotherapy. However, in Phase 1 human studies, entolimod induced a rapid neutralizing immune response, presumably due to immune memory from prior exposure to flagellated enterobacteria. To enable multi-dose applications, we used structure-guided reengineering to develop a next-generation, substantially deimmunized entolimod variant, GP532. GP532 induces TLR5-dependent NF-κB activation like entolimod but is smaller and has mutations eliminating an inflammasome-activating domain and key B- and T-cell epitopes. GP532 is resistant to human entolimod-neutralizing antibodies and shows reduced de novo immunogenicity. GP532 also has improved bioavailability, a stronger effect on key cytokine biomarkers, and a longer-lasting effect on NF-κB. Like entolimod, GP532 demonstrated potent prophylactic and therapeutic efficacy in mouse models of radiation-induced death and tissue damage. These results establish GP532 as an optimized TLR5 agonist suitable for multi-dose therapies and for patients with high titers of preexisting flagellin-neutralizing antibodies.

Indexed as

Signal TransductionCell Line, TumorHEK293 CellsHumansPeptidesToll-Like Receptor 5CBLB502PeptidesTLR5 protein, humanToll-Like Receptor 5

Identifiers

PMID33846531
PMCPMC8041767
OpenAlexW3154874027

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

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.