Evidence map›Paper›PMID 34675204›Full record

ArticleNature communications2021

Intracellular delivery of protein drugs with an autonomously lysing bacterial system reduces tumor growth and metastases.

Vishnu Raman, Nele Van Dessel, Christopher L Hall, Victoria E Wetherby, Samantha A Whitney, Emily L Kolewe, Shoshana M K Bloom, Abhinav Sharma, Jeanne A Hardy, Mathieu Bollen and 2 more

Open access · goldAbstract readEvaluation Study
PubMed Full text at PMC Publisher
In one paragraph

Article in Nature communications, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 81 papers.

0numbers the graph read from it
0cells of the map it votes in
81citing papers in PubMed
16.2field-weighted citation impact, top 1% 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

81 citing papers in PubMed, 154 citations in OpenAlex.

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21 more citing papers are in PubMed but not listed here.

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

12 authors at 2 institutions in 2 countries.

Vishnu Raman *Department of Chemical Engineering, University of Massachusetts, Amherst, Amherst, MA, USA.ORCID http://orcid.org/0000-0003-1179-8698
Nele Van Dessel *Department of Chemical Engineering, University of Massachusetts, Amherst, Amherst, MA, USA.
Christopher L HallDepartment of Chemical Engineering, University of Massachusetts, Amherst, Amherst, MA, USA.
Victoria E WetherbyErnest Pharmaceuticals, LLC, Hadley, MA, USA.
Samantha A WhitneyDepartment of Chemical Engineering, University of Massachusetts, Amherst, Amherst, MA, USA.
Emily L KoleweDepartment of Chemical Engineering, University of Massachusetts, Amherst, Amherst, MA, USA.
Shoshana M K BloomDepartment of Chemical Engineering, University of Massachusetts, Amherst, Amherst, MA, USA.ORCID http://orcid.org/0000-0003-0252-4513
Abhinav SharmaDepartment of Chemical Engineering, University of Massachusetts, Amherst, Amherst, MA, USA.ORCID http://orcid.org/0000-0002-6273-0119
Jeanne A HardyDepartment of Chemistry, University of Massachusetts, Amherst, Amherst, MA, USA.ORCID http://orcid.org/0000-0002-3406-7997
Mathieu BollenLaboratory of Biosignaling & Therapeutics, Department of Cellular and Molecular Medicine, KU Leuven, Leuven, Belgium.ORCID http://orcid.org/0000-0003-4975-1510
Aleyde Van EyndeLaboratory of Biosignaling & Therapeutics, Department of Cellular and Molecular Medicine, KU Leuven, Leuven, Belgium.ORCID http://orcid.org/0000-0002-3462-4976
Neil S ForbesDepartment of Chemical Engineering, University of Massachusetts, Amherst, Amherst, MA, USA. forbes@umass.edu.ORCID http://orcid.org/0000-0002-4745-753X
University of Massachusetts Amherst · USKU Leuven · BE

Funding

Targeting epigenetic regulators using bacterial macromolecule deliveryR01CA188382 · NCI · UNIVERSITY OF MASSACHUSETTS AMHERST · PI FORBES, NEIL S. · 2014 to 2018
$1.6M
Bacterial delivery of pro-apoptotic proteins in advanced hepatocellular carcinoma.R43CA250941 · NCI · ERNEST PHARMACEUTICALS, LLC · PI VAN DESSEL, NELE · 2020 to 2020
$284k
NCI NIH HHS R01 CA188382NCI NIH HHS R43 CA250941
6 · The paper itself

Abstract

Critical cancer pathways often cannot be targeted because of limited efficiency crossing cell membranes. Here we report the development of a Salmonella-based intracellular delivery system to address this challenge. We engineer genetic circuits that (1) activate the regulator flhDC to drive invasion and (2) induce lysis to release proteins into tumor cells. Released protein drugs diffuse from Salmonella containing vacuoles into the cellular cytoplasm where they interact with their therapeutic targets. Control of invasion with flhDC increases delivery over 500 times. The autonomous triggering of lysis after invasion makes the platform self-limiting and prevents drug release in healthy organs. Bacterial delivery of constitutively active caspase-3 blocks the growth of hepatocellular carcinoma and lung metastases, and increases survival in mice. This success in targeted killing of cancer cells provides critical evidence that this approach will be applicable to a wide range of protein drugs for the treatment of solid tumors.

Indexed as

AnimalsBacteriolysisCarcinoma, HepatocellularCaspase 3Cell Line, TumorCell ProliferationDrug Delivery SystemsFemaleHumansLiver NeoplasmsLung NeoplasmsMaleMiceSalmonellaSalmonella typhimuriumCASP3 protein, humanCaspase 3

Identifiers

PMID34675204
PMCPMC8531320
OpenAlexW3206763752

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.