Evidence map›Paper›PMID 39603241›Full record

ArticleCell chemical biology2024

Therapeutic induction of ferroptosis in tumors using PD-L1 targeting antibody nanogel conjugates.

Mengdie Wang, Theeraphop Prachyathipsakul, Christi A Silva, Choua Xiong, Shivam Goel, Hira Lal Goel, Emmet R Karner, Dimpi Mukhopadhyay, Prachi Gupta, Aniket Majee and 2 more

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In one paragraph

Article in Cell chemical biology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.

0numbers the graph read from it
0cells of the map it votes in
11citing papers in PubMed
–field-weighted citation impact
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

11 citing papers in PubMed.

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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

12 authors.

Mengdie WangDepartment of Molecular, Cell and Cancer Biology, University of Massachusetts Chan Medical School, Worcester, MA, USA.
Theeraphop PrachyathipsakulDepartment of Chemistry, University of Massachusetts, Amherst, MA, USA.
Christi A SilvaDepartment of Molecular, Cell and Cancer Biology, University of Massachusetts Chan Medical School, Worcester, MA, USA.
Choua XiongDepartment of Molecular, Cell and Cancer Biology, University of Massachusetts Chan Medical School, Worcester, MA, USA.
Shivam GoelDepartment of Molecular, Cell and Cancer Biology, University of Massachusetts Chan Medical School, Worcester, MA, USA.
Hira Lal GoelDepartment of Molecular, Cell and Cancer Biology, University of Massachusetts Chan Medical School, Worcester, MA, USA.
Emmet R KarnerDepartment of Molecular, Cell and Cancer Biology, University of Massachusetts Chan Medical School, Worcester, MA, USA.
Dimpi MukhopadhyayDepartment of Molecular, Cell and Cancer Biology, University of Massachusetts Chan Medical School, Worcester, MA, USA.
Prachi GuptaDepartment of Chemistry, University of Massachusetts, Amherst, MA, USA.
Aniket MajeeDepartment of Chemistry, University of Massachusetts, Amherst, MA, USA.
S ThayumanavanDepartment of Chemistry, University of Massachusetts, Amherst, MA, USA; Department of Biomedical Engineering, University of Massachusetts, Amherst, MA, USA. Electronic address: thai@umass.edu.
Arthur M MercurioDepartment of Molecular, Cell and Cancer Biology, University of Massachusetts Chan Medical School, Worcester, MA, USA. Electronic address: arthur.mercurio@umassmed.edu.

Funding

VEGF Signaling in Mammary TumorigenesisR01CA168464 · NCI · UNIV OF MASSACHUSETTS MED SCH WORCESTER · PI MERCURIO, ARTHUR M · 2012 to 2021
$3.7M
Protein-Induced Self-Assembly and Disassembly of Nanostructures Based on OligoR35GM136395 · NIGMS · UNIVERSITY OF MASSACHUSETTS AMHERST · PI Sankaran Thayumanavan · 2020 to 2026
$3.5M
Integrin Regulation of Non-apoptotic Death in Breast CancerR01CA218085 · NCI · UNIV OF MASSACHUSETTS MED SCH WORCESTER · PI MERCURIO, ARTHUR M · 2018 to 2022
$1.9M
Novel Therapeutic Approaches for Aggressive Prostate CancerR01CA276863 · NCI · UNIV OF MASSACHUSETTS MED SCH WORCESTER · PI Arthur M Mercurio · 2023 to 2026
$1.5M
NCI NIH HHS R01 CA168464NCI NIH HHS R01 CA218085NCI NIH HHS R01 CA276863NIGMS NIH HHS R35 GM136395
6 · The paper itself

Abstract

Although programmed cell death ligand 1 (PD-L1) is best known for its role in immune suppression, tumor-intrinsic functions are emerging. Here, we report that tumor cells that express PD-L1 are sensitive to ferroptosis inducers such as imidazole ketone erastin (IKE). PD-L1 promotes ferroptosis sensitivity because it suppresses SLC7A11 expression and diminishes glutathione levels. Although the use of anti-PD-L1 antibody drug conjugates (ADCs) could be effective for the delivery of ferroptosis inducers to specific tumor populations, the chemistry of most ferroptosis inducers precludes their incorporation in ADCs. To overcome this challenge, we synthesized an antibody nanogel conjugate (ANC) comprised of an anti-PD-L1 antibody conjugated to a nanogel encapsulated with IKE. This ANC targets PD-L1-expressing cells in vitro and in vivo and induces ferroptosis, resulting in tumor suppression. Importantly, this approach is superior to systemic administration of IKE because it enables enhanced delivery of IKE specifically to tumor cells and it requires lower drug doses for efficacy.

Indexed as

B7-H1 AntigenFerroptosisAnimalsCell Line, TumorFemaleHumansImidazolesImmunoconjugatesMiceNanogelsNeoplasmsPiperazinesB7-H1 AntigenCD274 protein, humanerastinImidazolesImmunoconjugatesNanogelsPiperazinesantibody-nanogel-conjugatescancerferroptosisnanogel

Identifiers

PMID39603241
PMCPMC11663111

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Registered trials

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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.