Evidence map›Paper›PMID 40389394›Full record

ArticleNature communications2025

Engineering anti-BCMA CAR T cells for enhancing myeloma killing efficacy via apoptosis regulation.

Thomas Kimman, Marta Cuenca, Ralph G Tieland, Dedeke Rockx-Brouwer, Jasmijn Janssen, Benjamin Motais, Anne Slomp, Corine Pleijte, Sabine Heijhuurs, Angelo D Meringa and 12 more

Erratum issuedAbstract read
In one paragraph

Article in Nature communications, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 9 papers.

0numbers the graph read from it
0cells of the map it votes in
9citing 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

9 citing papers in PubMed.

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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

22 authors.

Thomas Kimman *Center for Translational Immunology, University Medical Center Utrecht, Utrecht, Netherlands.
Marta Cuenca *Center for Translational Immunology, University Medical Center Utrecht, Utrecht, Netherlands.ORCID http://orcid.org/0000-0003-2261-7792
Ralph G TielandCenter for Translational Immunology, University Medical Center Utrecht, Utrecht, Netherlands.
Dedeke Rockx-BrouwerCenter for Translational Immunology, University Medical Center Utrecht, Utrecht, Netherlands.
Jasmijn JanssenDepartment of Cardiology, University Medical Center Utrecht, Utrecht, Netherlands.
Benjamin MotaisCenter for Translational Immunology, University Medical Center Utrecht, Utrecht, Netherlands.
Anne SlompCenter for Translational Immunology, University Medical Center Utrecht, Utrecht, Netherlands.
Corine PleijteCenter for Translational Immunology, University Medical Center Utrecht, Utrecht, Netherlands.
Sabine HeijhuursCenter for Translational Immunology, University Medical Center Utrecht, Utrecht, Netherlands.
Angelo D MeringaCenter for Translational Immunology, University Medical Center Utrecht, Utrecht, Netherlands.
Wendy BoschlooCenter for Translational Immunology, University Medical Center Utrecht, Utrecht, Netherlands.ORCID http://orcid.org/0000-0002-1599-1391
Douwe M T BosmaCenter for Translational Immunology, University Medical Center Utrecht, Utrecht, Netherlands.ORCID http://orcid.org/0000-0002-3500-8649
Sanne KroosCenter for Translational Immunology, University Medical Center Utrecht, Utrecht, Netherlands.ORCID http://orcid.org/0000-0001-8900-1285
Vania Lo PrestiCenter for Translational Immunology, University Medical Center Utrecht, Utrecht, Netherlands.
Joost P G SluijterDepartment of Cardiology, University Medical Center Utrecht, Utrecht, Netherlands.ORCID http://orcid.org/0000-0003-2088-9102
Stefan NierkensCenter for Translational Immunology, University Medical Center Utrecht, Utrecht, Netherlands.
Niels BovenschenCenter for Translational Immunology, University Medical Center Utrecht, Utrecht, Netherlands.ORCID http://orcid.org/0000-0002-8526-4456
Jürgen KuballCenter for Translational Immunology, University Medical Center Utrecht, Utrecht, Netherlands.ORCID http://orcid.org/0000-0002-3914-7806
Alain van MilDepartment of Cardiology, University Medical Center Utrecht, Utrecht, Netherlands.
Monique C MinnemaDepartment of Hematology, University Medical Centre Utrecht, Utrecht, Netherlands.
Zsolt SebestyénCenter for Translational Immunology, University Medical Center Utrecht, Utrecht, Netherlands.ORCID http://orcid.org/0000-0001-6184-7676
Victor PeperzakCenter for Translational Immunology, University Medical Center Utrecht, Utrecht, Netherlands. v.peperzak@umcutrecht.nl.ORCID http://orcid.org/0000-0002-9011-3820

Funding

KWF Kankerbestrijding (Dutch Cancer Society) 11270KWF Kankerbestrijding (Dutch Cancer Society) 13058KWF Kankerbestrijding (Dutch Cancer Society) 14459KWF Kankerbestrijding (Dutch Cancer Society) 15595
6 · The paper itself

Abstract

Clinical responses with chimeric antigen receptor (CAR) T cells are encouraging, but primary resistance and relapse after therapy prevent durable remission in many patients with cancer, with apoptosis resistance in cancer cells that limits killing by CAR T cells being a potential cause. Here we aim to boost tumor cell apoptosis induced by CAR T cells and find that anti-B cell maturation antigen (BCMA) CAR T cells over-expressing a granzyme B-NOXA fusion protein show improved killing of multiple myeloma (MM) cells in vitro and in xenograft mouse models in vivo. Mechanistically, such an enhancement is mediated by localizing NOXA to cytotoxic granules that are released into cancer cells upon contact. In MM cells, inhibition of MCL-1, an anti-apoptotic factor, by its natural ligand NOXA effectively induces apoptosis. Our data thus show that endowing granzyme B-NOXA expression to CAR T cells improves their killing efficacy, thereby presenting a potential generalizable enhancement for CAR T-mediated anti-cancer immunity.

Indexed as

ApoptosisB-Cell Maturation AntigenImmunotherapy, AdoptiveMultiple MyelomaReceptors, Chimeric AntigenT-LymphocytesAnimalsCell Line, TumorFemaleGranzymesHumansMiceMice, Inbred NODMyeloid Cell Leukemia Sequence 1 ProteinProto-Oncogene Proteins c-bcl-2Xenograft Model Antitumor AssaysB-Cell Maturation AntigenGranzymesGZMB protein, humanMCL1 protein, humanMyeloid Cell Leukemia Sequence 1 ProteinPMAIP1 protein, humanProto-Oncogene Proteins c-bcl-2Receptors, Chimeric Antigen

Identifiers

PMID40389394
PMCPMC12089368

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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.