Evidence map›Paper›PMID 38996027›Full record

ArticleScience advances2024

CAR memory-like NK cells targeting the membrane proximal domain of mesothelin demonstrate promising activity in ovarian cancer.

Mubin Tarannum, Khanhlinh Dinh, Juliana Vergara, Grace Birch, Yasmin Z Abdulhamid, Isabel E Kaplan, Oyku Ay, Andreia Maia, Owen Beaver, Michal Sheffer and 20 more

Abstract read
In one paragraph

Article in Science advances, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
35citing papers in PubMed, 1 pooled it
–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

35 citing papers in PubMed, 1 synthesis or guideline pooled it.

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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

30 authors.

Mubin TarannumDivision of Transplantation and Cellular Therapies, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.ORCID 0000-0002-4440-1565
Khanhlinh DinhDivision of Transplantation and Cellular Therapies, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.ORCID 0009-0005-1343-083X
Juliana VergaraDivision of Transplantation and Cellular Therapies, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.ORCID 0000-0002-1137-8098
Grace BirchDivision of Transplantation and Cellular Therapies, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.
Yasmin Z AbdulhamidDivision of Transplantation and Cellular Therapies, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.ORCID 0009-0000-9564-9424
Isabel E KaplanDivision of Transplantation and Cellular Therapies, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.ORCID 0009-0007-4781-2275
Oyku AyDivision of Transplantation and Cellular Therapies, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.
Andreia MaiaDivision of Transplantation and Cellular Therapies, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.ORCID 0000-0002-7860-6219
Owen BeaverDivision of Transplantation and Cellular Therapies, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.
Michal ShefferDivision of Transplantation and Cellular Therapies, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.ORCID 0000-0001-5934-9950
Roman ShapiroDivision of Transplantation and Cellular Therapies, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.ORCID 0000-0002-7622-8322
Alaa Kassim AliDivision of Transplantation and Cellular Therapies, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.
Han DongDepartment of Cancer Immunology and Virology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.ORCID 0009-0003-4975-8269
James Dongjoo HamKoch Institute for Integrative Cancer Research and Department of Biology, Massachusetts Institute of Technology, Cambridge, MA, USA.ORCID 0000-0003-0971-7940
Eden BobilevDivision of Transplantation and Cellular Therapies, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.
Sydney JamesLurie Family Imaging Center, Center for Biomedical Imaging in Oncology, Dana Farber Cancer Institute, Boston, MA, USA.
Amy B CameronLurie Family Imaging Center, Center for Biomedical Imaging in Oncology, Dana Farber Cancer Institute, Boston, MA, USA.ORCID 0009-0000-9609-8134
Quang-De NguyenLurie Family Imaging Center, Center for Biomedical Imaging in Oncology, Dana Farber Cancer Institute, Boston, MA, USA.ORCID 0000-0002-9043-4413
Suthakar GanapathyBelfer Center for Applied Cancer Science, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.
Chayapatou ChayawattoBelfer Center for Applied Cancer Science, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.
John KorethDivision of Transplantation and Cellular Therapies, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.
Cloud P PaweletzBelfer Center for Applied Cancer Science, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.
Prafulla C GokhaleBelfer Center for Applied Cancer Science, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.ORCID 0000-0002-1974-5921
David A BarbieBelfer Center for Applied Cancer Science, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.
Ursula A MatulonisDivision of Gynecologic Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.
Robert J SoifferDivision of Transplantation and Cellular Therapies, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.ORCID 0000-0002-5810-1192
Jerome RitzDivision of Transplantation and Cellular Therapies, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.ORCID 0000-0001-5526-4669
Rebecca L PorterDivision of Gynecologic Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.ORCID 0000-0002-4848-1275
Jianzhu ChenKoch Institute for Integrative Cancer Research and Department of Biology, Massachusetts Institute of Technology, Cambridge, MA, USA.ORCID 0000-0002-5687-6154
Rizwan RomeeDivision of Transplantation and Cellular Therapies, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.ORCID 0000-0001-9077-4736

Funding

Single Cell and ImmunogenomicsP01CA229092 · NCI · DANA-FARBER CANCER INST · PI KIM, HAESOOK T · 2019 to 2023
$13.8M
Project 2: Combined personal neoantigen-targeting cancer vaccines with immune checkpoint blockade for ovarian cancerP50CA240243 · NCI · DANA-FARBER CANCER INST · PI CASTRO, CESAR M · 2020 to 2024
$11.5M
NCI NIH HHS P01 CA229092NCI NIH HHS P50 CA240243
6 · The paper itself

Abstract

Epithelial ovarian cancer (EOC) remains one of the most lethal gynecological cancers. Cytokine-induced memory-like (CIML) natural killer (NK) cells have shown promising results in preclinical and early-phase clinical trials. In the current study, CIML NK cells demonstrated superior antitumor responses against a panel of EOC cell lines, increased expression of activation receptors, and up-regulation of genes involved in cell cycle/proliferation and down-regulation of inhibitory/suppressive genes. CIML NK cells transduced with a chimeric antigen receptor (CAR) targeting the membrane-proximal domain of mesothelin (MSLN) further improved the antitumor responses against MSLN-expressing EOC cells and patient-derived xenograft tumor cells. CAR arming of the CIML NK cells subtanstially reduced their dysfunction in patient-derived ascites fluid with transcriptomic changes related to altered metabolism and tonic signaling as potential mechanisms. Lastly, the adoptive transfer of MSLN-CAR CIML NK cells demonstrated remarkable inhibition of tumor growth and prevented metastatic spread in xenograft mice, supporting their potential as an effective therapeutic strategy in EOC.

Indexed as

Killer Cells, NaturalMesothelinOvarian NeoplasmsAnimalsCarcinoma, Ovarian EpithelialCell Line, TumorFemaleGPI-Linked ProteinsHumansImmunologic MemoryImmunotherapy, AdoptiveMiceProtein DomainsReceptors, Chimeric AntigenXenograft Model Antitumor AssaysGPI-Linked ProteinsMesothelinMSLN protein, humanMsln protein, mouseReceptors, Chimeric Antigen

Identifiers

PMID38996027
PMCPMC11244547

What Socratic holds

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LicenceCC BY-NC
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 Socratic graph.