Evidence map›Paper›PMID 34889072›Full record

ArticleAdvanced healthcare materials2022

Arming Immune Cell Therapeutics with Polymeric Prodrugs.

Ciana L López, Katherine J Brempelis, James F Matthaei, Kate S Montgomery, Selvi Srinivasan, Debashish Roy, Fei Huang, Shannon A Kreuser, Jennifer L Gardell, Ian Blumenthal and 4 more

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 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed
0.2field-weighted citation impact, top 44% 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

6 citing papers in PubMed, 4 citations in OpenAlex.

  1. Review
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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 5 institutions in 3 countries.

Ciana L LópezDepartment of Bioengineering, University of Washington, Seattle, WA, 98195, USA.ORCID 0000-0003-3638-6454
Katherine J BrempelisBen Towne Center for Childhood Cancer Research, Seattle Children's Research Institute, Seattle, WA, 98101, USA.ORCID 0000-0002-9255-2608
James F MatthaeiSeattle Children's Therapeutics, Seattle Children's Research Institute, Seattle, WA, 98101, USA.
Kate S MontgomeryDepartment of Bioengineering, University of Washington, Seattle, WA, 98195, USA.
Selvi SrinivasanDepartment of Bioengineering, University of Washington, Seattle, WA, 98195, USA.
Debashish RoyDepartment of Bioengineering, University of Washington, Seattle, WA, 98195, USA.
Fei HuangCSIRO Manufacturing, Bag 10, Bayview Avenue, Clayton, VIC, 3168, Australia.
Shannon A KreuserBen Towne Center for Childhood Cancer Research, Seattle Children's Research Institute, Seattle, WA, 98101, USA.
Jennifer L GardellBen Towne Center for Childhood Cancer Research, Seattle Children's Research Institute, Seattle, WA, 98101, USA.
Ian BlumenthalDepartment of Bioengineering, University of Washington, Seattle, WA, 98195, USA.
John ChiefariCSIRO Manufacturing, Bag 10, Bayview Avenue, Clayton, VIC, 3168, Australia.
Michael C JensenDepartment of Bioengineering, University of Washington, Seattle, WA, 98195, USA.
Courtney A CraneBen Towne Center for Childhood Cancer Research, Seattle Children's Research Institute, Seattle, WA, 98101, USA.
Patrick S StaytonDepartment of Bioengineering, University of Washington, Seattle, WA, 98195, USA.ORCID 0000-0001-6939-6371
Seattle Children's Hospital · USUniversity of Washington · USCSIRO Manufacturing · AUCape Town HVTN Immunology Laboratory / Hutchinson Centre Research Institute of South Africa · ZASeattle Children's Hospital · US

Funding

Engineered Antimicrobial Platform to Target Pulmonary Intracellular InfectionsR01AI134729 · NIAID · UNIVERSITY OF WASHINGTON · PI Shawn J. Skerrett, Patrick S. Stayton · 2018 to 2026
$4.9M
Genetically engineered macrophages to treat pulmonary infectionsR21AI149400 · NIAID · UNIVERSITY OF WASHINGTON · PI SKERRETT, SHAWN J., WEST, TIMOTHY EOIN · 2020 to 2021
$493k
NIAID NIH HHS R01 AI134729NIAID NIH HHS R21 AI149400
6 · The paper itself

Abstract

Engineered immune cells are an exciting therapeutic modality, which survey and attack tumors. Backpacking strategies exploit cell targeting capabilities for delivery of drugs to combat tumors and their immune-suppressive environments. Here, a new platform for arming cell therapeutics through dual receptor and polymeric prodrug engineering is developed. Macrophage and T cell therapeutics are engineered to express a bioorthogonal single chain variable fragment receptor. The receptor binds a fluorescein ligand that directs cell loading with ligand-tagged polymeric prodrugs, termed "drugamers." The fluorescein ligand facilitates stable binding of drugamer to engineered macrophages over 10 days with 80% surface retention. Drugamers also incorporate prodrug monomers of the phosphoinositide-3-kinase inhibitor, PI-103. The extended release of PI-103 from the drugamer sustains antiproliferative activity against a glioblastoma cell line compared to the parent drug. The versatility and modularity of this cell arming system is demonstrated by loading T cells with a second fluorescein-drugamer. This drugamer incorporates a small molecule estrogen analog, CMP8, which stabilizes a degron-tagged transgene to provide temporal regulation of protein activity in engineered T cells. These results demonstrate that this bioorthogonal receptor and drugamer system can be used to arm multiple immune cell classes with both antitumor and transgene-activating small molecule prodrugs.

Indexed as

NeoplasmsProdrugsFluoresceinsHumansLigandsPolymersFluoresceinsLigandsPolymersProdrugscell backpackingcell-mediated targetingmacrophagespolymeric prodrugssolid tumors

Identifiers

PMID34889072
PMCPMC9847575
OpenAlexW4200260831

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.