Evidence map›Paper›PMID 38296597›Full record

ArticleJournal for immunotherapy of cancer2024

PD-1 checkpoint inhibition enhances the antilymphoma activity of CD19-CAR-iNKT cells that retain their ability to prevent alloreactivity.

Emmanuelle Moraes Ribeiro, Kathy-Ann Secker, Ana-Maria Nitulescu, Rebekka Schairer, Hildegard Keppeler, Anton Wesle, Hannes Schmid, Anita Schmitt, Brigitte Neuber, Daniela Chmiest and 8 more

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Journal for immunotherapy of cancer, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed
2.3field-weighted citation impact, top 11% of its field
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

6 citing papers in PubMed, 8 citations in OpenAlex.

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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

18 authors at 5 institutions in 2 countries.

Emmanuelle Moraes RibeiroDepartment of Hematology, Oncology, Clinical Immunology and Rheumatology, University Hospital Tübingen, Tübingen, Germany.ORCID 0000-0002-0420-5818
Kathy-Ann SeckerDepartment of Hematology, Oncology, Clinical Immunology and Rheumatology, University Hospital Tübingen, Tübingen, Germany.
Ana-Maria NitulescuDepartment of Hematology, Oncology, Clinical Immunology and Rheumatology, University Hospital Tübingen, Tübingen, Germany.ORCID 0009-0008-0714-6607
Rebekka SchairerDepartment of Hematology, Oncology, Clinical Immunology and Rheumatology, University Hospital Tübingen, Tübingen, Germany.
Hildegard KeppelerDepartment of Hematology, Oncology, Clinical Immunology and Rheumatology, University Hospital Tübingen, Tübingen, Germany.
Anton WesleDepartment of Hematology, Oncology, Clinical Immunology and Rheumatology, University Hospital Tübingen, Tübingen, Germany.
Hannes SchmidDepartment of Hematology, Oncology, Clinical Immunology and Rheumatology, University Hospital Tübingen, Tübingen, Germany.
Anita SchmittDepartment of Oncology, Hematology and Rheumatology, University Hospital Heidelberg, Heidelberg, Germany.
Brigitte NeuberDepartment of Oncology, Hematology and Rheumatology, University Hospital Heidelberg, Heidelberg, Germany.
Daniela ChmiestDepartment of Immunobiology, University of Lausanne, Lausanne, Switzerland.
Silvia PodaviniDepartment of Immunobiology, University of Lausanne, Lausanne, Switzerland.
Melanie MärklinClinical Collaboration Unit Translational Immunology, German Cancer Consortium (DKTK), Department of Internal Medicine, University Hospital Tübingen, Tübingen, Germany.ORCID 0000-0002-2920-3894
Boris KlimovichClinical Collaboration Unit Translational Immunology, German Cancer Consortium (DKTK), Department of Internal Medicine, University Hospital Tübingen, Tübingen, Germany.
Michael SchmittDepartment of Oncology, Hematology and Rheumatology, University Hospital Heidelberg, Heidelberg, Germany.
Fulya KorkmazDepartment of Hematology, Oncology, Clinical Immunology and Rheumatology, University Hospital Tübingen, Tübingen, Germany.
Claudia LengerkeDepartment of Hematology, Oncology, Clinical Immunology and Rheumatology, University Hospital Tübingen, Tübingen, Germany.
Corina SchneidawindDepartment of Hematology, Oncology, Clinical Immunology and Rheumatology, University Hospital Tübingen, Tübingen, Germany.
Dominik SchneidawindDepartment of Hematology, Oncology, Clinical Immunology and Rheumatology, University Hospital Tübingen, Tübingen, Germany dominik.schneidawind@usz.ch.ORCID 0000-0002-2672-431X
University Children's Hospital Tübingen · DEHeidelberg University · DEDeutschen Konsortium für Translationale Krebsforschung · DEUniversity Hospital of Zurich · CHUniversity of Lausanne · CH

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundRelapse and graft-versus-host disease (GVHD) are the main causes of death after allogeneic hematopoietic cell transplantation (HCT). Preclinical murine models and clinical data suggest that invariant natural killer T (iNKT) cells prevent acute and chronic GVHD. In addition, iNKT cells are crucial for efficient immune responses against malignancies and contribute to reduced relapse rates after transplantation. Chimeric antigen receptors (CAR) redirect effector cells to cell surface antigens and enhance killing of target cells. With this study, we aimed to combine enhanced cytotoxicity of CD19-CAR-iNKT cells against lymphoma cells with their tolerogenic properties.

methodsiNKT cells were isolated from peripheral blood mononuclear cells and transduced with an anti-CD19-CAR retrovirus. After in vitro expansion, the functionality of CD19-CAR-iNKT cells was assessed by flow cytometry, image stream analysis and multiplex analysis in single-stimulation or repeated-stimulation assays. Moreover, the immunoregulatory properties of CD19-CAR-iNKT cells were analyzed in apoptosis assays and in mixed lymphocyte reactions. The effect of checkpoint inhibition through nivolumab was analyzed in these settings.

resultsIn this study, we could show that the cytotoxicity of CD19-CAR-iNKT cells was mediated either through engagement of their CAR or their invariant T-cell receptor, which may circumvent loss of response through antigen escape. However, encounter of CD19-CAR-iNKT cells with their target induced a phenotype of exhaustion. Consequently, checkpoint inhibition increased cytokine release, cytotoxicity and survival of CD19-CAR-iNKT cells. Additionally, they showed robust suppression of alloreactive immune responses.

conclusionIn this work, we demonstrate that CAR-iNKT cells are a powerful cytotherapeutic option to prevent or treat relapse while potentially reducing the risk of GVHD after allogeneic HCT.

Indexed as

Graft vs Host DiseaseNatural Killer T-CellsReceptors, Chimeric AntigenAnimalsAntigens, CD19HumansMiceProgrammed Cell Death 1 ReceptorRecurrenceAntigens, CD19Programmed Cell Death 1 ReceptorReceptors, Chimeric AntigenImmune Checkpoint InhibitorsImmunotherapyNatural Killer T-CellsReceptors, Chimeric AntigenTransplantation Immunology

Identifiers

PMID38296597
PMCPMC10831439
OpenAlexW4391406798

What OpenQuestion holds

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LicenceCC BY
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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.