Evidence map›Paper›PMID 42733076›Full record

ArticleNature communications2026

Enhancing iNKT cell immunotherapy through the integration of optimized CAR endodomains and iNKT engagers.

Kanagaraju Ponnusamy, Klesti Karaxhuku, Yuchao Jiang, Lyra Randzavola, Hongwei Ren, Ilia Leontari, Bryan Lye, Mehmood Zaidi, Edward J Bartlett, Edward W Tate and 11 more

Abstract read
In one paragraph

Article in Nature communications, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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

0 citing papers in PubMed.

No citing paper in PubMed yet.

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

21 authors.

Kanagaraju Ponnusamy *Hugh & Josseline Langmuir Centre for Myeloma Research, Centre for Haematology, Department of Immunology and Inflammation, Imperial College London, London, UK. k.ponnusamy@imperial.ac.uk.ORCID http://orcid.org/0000-0002-6618-9104
Klesti Karaxhuku *Hugh & Josseline Langmuir Centre for Myeloma Research, Centre for Haematology, Department of Immunology and Inflammation, Imperial College London, London, UK.
Yuchao JiangHugh & Josseline Langmuir Centre for Myeloma Research, Centre for Haematology, Department of Immunology and Inflammation, Imperial College London, London, UK.ORCID http://orcid.org/0000-0002-4465-0457
Lyra RandzavolaCentre for Haematology, Department of Immunology and Inflammation, Imperial College London, London, UK.
Hongwei RenCentre for Haematology, Department of Immunology and Inflammation, Imperial College London, London, UK.
Ilia LeontariHugh & Josseline Langmuir Centre for Myeloma Research, Centre for Haematology, Department of Immunology and Inflammation, Imperial College London, London, UK.
Bryan LyeCentre for Haematology, Department of Immunology and Inflammation, Imperial College London, London, UK.ORCID http://orcid.org/0000-0001-5058-7469
Mehmood ZaidiHugh & Josseline Langmuir Centre for Myeloma Research, Centre for Haematology, Department of Immunology and Inflammation, Imperial College London, London, UK.
Edward J BartlettDepartment of Chemistry, Natural Sciences, Imperial College London, London, UK.
Edward W TateDepartment of Chemistry, Natural Sciences, Imperial College London, London, UK.ORCID http://orcid.org/0000-0003-2213-5814
Vasileios PardalisCentre for Haematology, Department of Immunology and Inflammation, Imperial College London, London, UK.
Dimitrios LeonardosHugh & Josseline Langmuir Centre for Myeloma Research, Centre for Haematology, Department of Immunology and Inflammation, Imperial College London, London, UK.
Reza NadafiLumicks, Amsterdam, Netherlands.
Irene SarkarLumicks, Amsterdam, Netherlands.
Rogier M ReijmersLumicks, Amsterdam, Netherlands.
Marco BuaDepartment of Haematology, Hammersmith Hospital, Imperial College Healthcare NHS Trust, London, UK.
Maria AttaDepartment of Haematology, Hammersmith Hospital, Imperial College Healthcare NHS Trust, London, UK.
Alexia KatsarouHugh & Josseline Langmuir Centre for Myeloma Research, Centre for Haematology, Department of Immunology and Inflammation, Imperial College London, London, UK.
Irene Ag RobertsDepartment of Paediatrics, University of Oxford, Oxford, UK.
Aristeidis ChaidosHugh & Josseline Langmuir Centre for Myeloma Research, Centre for Haematology, Department of Immunology and Inflammation, Imperial College London, London, UK.ORCID http://orcid.org/0000-0003-1453-8576
Anastasios KaradimitrisHugh & Josseline Langmuir Centre for Myeloma Research, Centre for Haematology, Department of Immunology and Inflammation, Imperial College London, London, UK. a.karadimitris@imperial.ac.uk.ORCID http://orcid.org/0000-0002-9566-9780

Funding

Cancer Research UK (CRUK) 100058Kay Kendall Leukaemia Fund (KKLF) KKL1360
6 · The paper itself

Abstract

iNKT cells are emerging as a highly promising immunotherapy platform for the treatment of cancer. To maximise the anti-cancer activity of CAR-iNKT against the blood cancer multiple myeloma we investigated optimal CAR designs and their combination with new iNKT-specific engagers. We find that amongst five different CAR endodomains, underpinned by increased avidity and a cross talk between Plexin D1 on CAR-iNKT and Semaphorin 4 A on myeloma cells, BCMA CD28z CAR-iNKT exert the highest anti-myeloma activity. Notably, CD28z CAR-iNKT outperform their CAR-T counterparts. To expand the anti-myeloma potential of CAR-iNKT, we designed and validated a high efficacy BCMA iNKT-specific engager which exerts significant anti-myeloma activity in conjunction with adoptively transferred iNKT cells. Finally, combined, dual target therapy with FCRL5 CAR-iNKT and BCMA iNKT engagers outperforms FCRL5 CAR-iNKT and limits immune escape of FCRL5-negative myeloma. Thus, optimised iNKT-based, dual-target, dual-modality immunotherapy has enhanced anti-tumor activity against multiple myeloma and potentially other malignancies.

Indexed as

Immunotherapy, AdoptiveMultiple MyelomaNatural Killer T-CellsReceptors, Chimeric AntigenAnimalsCell Line, TumorHumansImmunotherapyMiceReceptors, Chimeric Antigen

Identifiers

PMID42733076
PMCPMC13572498

What OpenQuestion holds

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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.