Evidence map›Paper›PMID 34738725›Full record

ArticleAdvanced healthcare materials2022

Engineered Bacteria Enhance Immunotherapy and Targeted Therapy through Stromal Remodeling of Tumors.

Shindu C Thomas, Tushar Madaan, Nitin S Kamble, Nabil A Siddiqui, Giovanni M Pauletti, Nalinikanth Kotagiri

Open access · greenAbstract read
In one paragraph

Article in Advanced healthcare materials, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 51 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
51citing papers in PubMed, 1 pooled it
6.8field-weighted citation impact, top 2% 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

51 citing papers in PubMed, 1 synthesis or guideline pooled it, 80 citations in OpenAlex.

  1. Pooled it
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  3. Review
  4. Article
  5. Living Microbial Drugs.Chemistry (Weinheim an der Bergstrasse, Germany) · 2026
    Review
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  7. Bacterial Outer Membrane Vesicles in Potentiating Cancer Vaccines: Progress and Prospects.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026
    Review
  8. Microbial medicines: Unlocking the therapeutic potential of the microbiome in cancer treatment.Journal of controlled release : official journal of the Controlled Release Society · 2026
    Review
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  10. Review
  11. Review
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  13. Article
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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.

Shindu C ThomasDivision of Pharmaceutical Sciences, James L. Winkle College of Pharmacy, University of Cincinnati, 231 Albert Sabin Way, Cincinnati, OH, 45267, USA.
Tushar MadaanDivision of Pharmaceutical Sciences, James L. Winkle College of Pharmacy, University of Cincinnati, 231 Albert Sabin Way, Cincinnati, OH, 45267, USA.
Nitin S KambleDivision of Pharmaceutical Sciences, James L. Winkle College of Pharmacy, University of Cincinnati, 231 Albert Sabin Way, Cincinnati, OH, 45267, USA.
Nabil A SiddiquiDivision of Pharmaceutical Sciences, James L. Winkle College of Pharmacy, University of Cincinnati, 231 Albert Sabin Way, Cincinnati, OH, 45267, USA.
Giovanni M PaulettiDepartment of Pharmaceutical and Administrative Sciences, University of Health Sciences and Pharmacy in St. Louis, 1 Pharmacy Place, St. Louis, MO, 63110, USA.
Nalinikanth KotagiriDivision of Pharmaceutical Sciences, James L. Winkle College of Pharmacy, University of Cincinnati, 231 Albert Sabin Way, Cincinnati, OH, 45267, USA.ORCID 0000-0003-0066-4563
University of Cincinnati · USUniversity of Health Sciences and Pharmacy · US

Funding

A Synthetic Approach for Bacterial-Mammalian Cell BindingR21GM137321 · NIGMS · UNIVERSITY OF CINCINNATI · PI KOTAGIRI, NALINIKANTH · 2020 to 2021
$450k
NIGMS NIH HHS R21 GM137321
6 · The paper itself

Abstract

Desmoplastic solid tumors are characterized by the rapid build-up of extracellular matrix (ECM) macromolecules, such as hyaluronic acid (HA). The resulting physiological barrier prevents the infiltration of immune cells and also impedes the delivery of anticancer agents. The development of a hypervesiculating Escherichia coli Nissle (ΔECHy) based tumor targeting bacterial system capable of distributing a fusion peptide, cytolysin A (ClyA)-hyaluronidase (Hy) via outer membrane vesicles (OMVs) is reported. The capability of targeting hypoxic tumors, manufacturing recombinant proteins in situ and the added advantage of an on-site OMV based distribution system makes the engineered bacterial vector a unique candidate for peptide delivery. The HA degrading potential of Hy for stromal modulation is combined with the cytolytic activity of ClyA followed by testing it within syngeneic cancer models. ΔECHy is combined with immune checkpoint antibodies and tyrosine kinase inhibitors (TKIs) to demonstrate that remodeling the tumor stroma results in the improvement of immunotherapy outcomes and enhancing the efficacy of biological signaling inhibitors. The biocompatibility of ΔECHy is also investigated to show that the engineered bacteria are effectively cleared, elicit minimal inflammatory and immune responses, and therefore could be a reliable candidate as a live biotherapeutic.

Indexed as

Escherichia coliNeoplasmsBacteriaHumansImmunologic FactorsImmunotherapyImmunologic Factorsdesmoplastic cancerEscherichia coli Nisslehyaluronic acidimmunotherapyouter membrane vesiclestromal remodelingtargeted therapy

Identifiers

PMID34738725
PMCPMC8770579
OpenAlexW3211081549

What OpenQuestion holds

Textmetadata
LicenceTDM
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.