Evidence map›Paper›PMID 39980195›Full record

ArticleMolecular therapy : the journal of the American Society of Gene Therapy2025

ZP4: A novel target for CAR-T cell therapy in triple negative breast cancer.

Lauren K Somes, Jonathan T Lei, Xinpei Yi, Diego F Chamorro, Paul Shafer, Ahmed Z Gad, Lacey E Dobrolecki, Emily Madaras, Nabil Ahmed, Michael T Lewis and 2 more

Abstract read
In one paragraph

Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing 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

3 citing papers in PubMed.

  1. Review
  2. Review
  3. Review
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.

Lauren K SomesCenter for Cell and Gene Therapy, Baylor College of Medicine, Houston, TX 77030, USA. Electronic address: lauren.somes@bcm.edu.
Jonathan T LeiLester and Sue Smith Breast Center, Baylor College of Medicine, Houston, TX 77030, USA; Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA.
Xinpei YiLester and Sue Smith Breast Center, Baylor College of Medicine, Houston, TX 77030, USA; Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA.
Diego F ChamorroCenter for Cell and Gene Therapy, Baylor College of Medicine, Houston, TX 77030, USA.
Paul ShaferCenter for Cell and Gene Therapy, Baylor College of Medicine, Houston, TX 77030, USA.
Ahmed Z GadCenter for Cell and Gene Therapy, Baylor College of Medicine, Houston, TX 77030, USA.
Lacey E DobroleckiLester and Sue Smith Breast Center, Baylor College of Medicine, Houston, TX 77030, USA; Dan L. Duncan Cancer Center, Baylor College of Medicine, Houston, TX 77030, USA; Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX 77030, USA.
Emily MadarasCenter for Cell and Gene Therapy, Baylor College of Medicine, Houston, TX 77030, USA.
Nabil AhmedCenter for Cell and Gene Therapy, Baylor College of Medicine, Houston, TX 77030, USA.
Michael T LewisLester and Sue Smith Breast Center, Baylor College of Medicine, Houston, TX 77030, USA; Dan L. Duncan Cancer Center, Baylor College of Medicine, Houston, TX 77030, USA; Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX 77030, USA.
Bing ZhangLester and Sue Smith Breast Center, Baylor College of Medicine, Houston, TX 77030, USA; Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA.
Valentina HoyosCenter for Cell and Gene Therapy, Baylor College of Medicine, Houston, TX 77030, USA.

Funding

Training In Cell and Gene TherapyT32HL092332 · NHLBI · BAYLOR COLLEGE OF MEDICINE · PI MALCOLM K. BRENNER, Bruno Di Stefano · 2008 to 2026
$6.9M
Translating Pediatric Cancer Proteogenomic Data into Biological and Clinical InsightsU24CA271076 · NCI · BAYLOR COLLEGE OF MEDICINE · PI Bing Zhang · 2022 to 2026
$5.0M
The Clinical Translational Research Certificate of Added Qualification ProgramT32GM136554 · NIGMS · BAYLOR COLLEGE OF MEDICINE · PI Melissa Suter, IGNATIA B VAN DEN VEYVER · 2020 to 2026
$3.0M
Proteogenomics-driven therapeutic discovery in hepatocellular carcinomaR01CA245903 · NCI · BAYLOR COLLEGE OF MEDICINE · PI ZHANG, BING · 2020 to 2024
$1.0M
High Memory High-Performance Computer Cluster for Biomedical ResearchS10OD032185 · OD · BAYLOR COLLEGE OF MEDICINE · PI HILSENBECK, SUSAN G. · 2022 to 2022
$596k
NCI NIH HHS R01 CA245903NCI NIH HHS U24 CA271076NHLBI NIH HHS T32 HL092332NIGMS NIH HHS T32 GM136554NIH HHS S10 OD032185
6 · The paper itself

Abstract

Triple-negative breast cancer (TNBC) remains one of the most challenging subtypes of breast cancer to treat due to a lack of effective targeted therapies. Chimeric antigen receptor (CAR)-T cells hold promise, but their efficacy in solid tumors is often limited by on-target/off-tumor toxicities. Through comprehensive bioinformatic analysis of public RNA and proteomic data, we identified zona pellucida glycoprotein 4 (ZP4) as a novel target for TNBC. ZP4 RNA and protein were detected in a subset of TNBC patient samples and patient-derived xenograft (PDX) models, with expression otherwise restricted to oocytes. We generated 89 ZP4-specific novel monoclonal antibodies and used the single-chain variable fragment (scFv) antigen binding domains from the top three candidates to engineer CAR constructs. ZP4 CAR-T cells demonstrated efficacy against ZP4-expressing TNBC cells and PDX models. Additionally, we found that variations in the scFv antigen binding domain significantly influence CAR-T cell function.

Indexed as

Immunotherapy, AdoptiveReceptors, Chimeric AntigenTriple Negative Breast NeoplasmsZona Pellucida GlycoproteinsAnimalsCell Line, TumorDisease Models, AnimalFemaleHumansMiceSingle-Chain AntibodiesXenograft Model Antitumor AssaysReceptors, Chimeric AntigenSingle-Chain AntibodiesZona Pellucida Glycoproteinsbreast cancerCAR-T cellscellular immunotherapiesmonoclonal antibodiestranslational researchxenograft modelsZP4

Identifiers

PMID39980195
PMCPMC11997509

What OpenQuestion holds

Textmetadata
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.