Evidence map›Paper›PMID 41802812›Full record

ArticleJournal for immunotherapy of cancer2026

Targeting endosomal trafficking-mediated antigen escape to resensitize myeloma to CAR-T therapy.

Zhuning Wang, Guanli Wang, Yujie Liu, Yufei Zhao, Shushan Guo, Yicun Yang, Qikai Zhang, Chaolu Hu, Shuaikang Chang, Xiaosong Wu and 5 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Journal for immunotherapy of cancer, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing 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

1 citing paper in PubMed.

  1. 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

15 authors.

Zhuning Wang *Department of Hematology, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, Shanghai, China.
Guanli Wang *Department of Hematology, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, Shanghai, China.
Yujie Liu *Department of Hematology, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, Shanghai, China.
Yufei Zhao *Department of Hematology, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, Shanghai, China.
Shushan GuoDepartment of Hematology, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, Shanghai, China.
Yicun YangDepartment of Hematology, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, Shanghai, China.
Qikai ZhangDepartment of Hematology, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, Shanghai, China.
Chaolu HuDepartment of Hematology, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, Shanghai, China.
Shuaikang ChangDepartment of Hematology, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, Shanghai, China.
Xiaosong WuDepartment of Hematology, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, Shanghai, China.
Dong AnDepartment of Hematology, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, Shanghai, China.
Huifang HuDepartment of Hematology, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, Shanghai, China.
Haiyan CaiDepartment of Hematology, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, Shanghai, China.
Li ZhangDepartment of Hematology, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, Shanghai, China shijumei@tongji.edu.cn 21310130@tongji.edu.cn.
Jumei ShiDepartment of Hematology, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, Shanghai, China shijumei@tongji.edu.cn 21310130@tongji.edu.cn.ORCID http://orcid.org/0000-0002-8553-4559

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundAntigen escape is one of the leading causes of relapse following chimeric antigen receptor (CAR)-T therapy, particularly in multiple myeloma. A critical gap persists in understanding the tumor-intrinsic pathways that trigger antigen loss, insight essential for devising strategies to resensitize tumors to immune attack. We identify a previously uncharacterized post-translational mechanism centered on the metabolic enzyme ribonucleotide reductase subunit M2 (RRM2), termed trafficking-mediated antigen escape, to enhance cellular therapy efficacy.

methodsWe combined single-cell RNA sequencing analysis with multiplex immunofluorescence to identify a clinically relevant RRM2

resultsSingle-cell analysis uncovered a clinically prevalent RRM2

conclusionsOur study establishes RRM2-driven trafficking as a novel and targetable mechanism of antigen escape in CAR-T therapy. By repurposing osalmid to restore MICA/B surface presentation, we provide a clinically translatable strategy that specifically potentiates NKG2D CAR-T cell efficacy in multiple myeloma and could potentially enhance the efficacy of CAR-T across diverse antigens. This work highlights the therapeutic potential of modulating intracellular trafficking to overcome resistance in cellular immunotherapy.

Indexed as

EndosomesImmunotherapy, AdoptiveMultiple MyelomaReceptors, Chimeric AntigenTumor EscapeAnimalsCell Line, TumorHumansMicerab7 GTP-Binding ProteinsRibonucleoside Diphosphate ReductaseXenograft Model Antitumor Assaysrab7 GTP-Binding ProteinsReceptors, Chimeric AntigenRibonucleoside Diphosphate Reductaseribonucleotide reductase M2Chimeric antigen receptor - CARImmunotherapyMultiple Myeloma

Identifiers

PMID41802812
PMCPMC12983694

What OpenQuestion holds

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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.