Evidence map›Paper›PMID 33156338›Full record

ArticleThe Journal of experimental medicine2021

Optimized gene engineering of murine CAR-T cells reveals the beneficial effects of IL-15 coexpression.

Evripidis Lanitis, Giorgia Rota, Paris Kosti, Catherine Ronet, Aodrenn Spill, Bili Seijo, Pedro Romero, Denarda Dangaj, George Coukos, Melita Irving

Open access · hybridAbstract read
In one paragraph

Article in The Journal of experimental medicine, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 112 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
112citing papers in PubMed, 1 pooled it
6.5field-weighted citation impact, top 2% 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

112 citing papers in PubMed, 1 synthesis or guideline pooled it, 151 citations in OpenAlex.

  1. Pooled it
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  4. IL-15 and IL-21 synergy improves anti-tumor efficacy of iPSC-derived cytotoxic T cells in solid tumors.Molecular therapy : the journal of the American Society of Gene Therapy · 2026
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  16. Generation and Characterization of CAR-T Cells.Methods in molecular biology (Clifton, N.J.) · 2026
    Article
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  20. Article

52 more citing papers are in PubMed but not listed here.

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

10 authors at 2 institutions in 1 country.

Evripidis LanitisDepartment of Oncology, Ludwig Institute for Cancer Research Lausanne, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland.
Giorgia RotaDepartment of Oncology, Ludwig Institute for Cancer Research Lausanne, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland.
Paris KostiDepartment of Oncology, Ludwig Institute for Cancer Research Lausanne, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland.
Catherine RonetDepartment of Oncology, Ludwig Institute for Cancer Research Lausanne, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland.
Aodrenn Spill
Bili SeijoDepartment of Oncology, Ludwig Institute for Cancer Research Lausanne, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland.
Pedro RomeroDepartment of Oncology, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland.
Denarda DangajDepartment of Oncology, Ludwig Institute for Cancer Research Lausanne, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland.
George CoukosDepartment of Oncology, Ludwig Institute for Cancer Research Lausanne, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland.
Melita IrvingDepartment of Oncology, Ludwig Institute for Cancer Research Lausanne, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland.
Ludwig Cancer Research · CHUniversity of Lausanne · CH

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Limited clinical benefit has been demonstrated for chimeric antigen receptor (CAR) therapy of solid tumors, but coengineering strategies to generate so-called fourth-generation (4G) CAR-T cells are advancing toward overcoming barriers in the tumor microenvironment (TME) for improved responses. In large part due to technical challenges, there are relatively few preclinical CAR therapy studies in immunocompetent, syngeneic tumor-bearing mice. Here, we describe optimized methods for the efficient retroviral transduction and expansion of murine T lymphocytes of a predominantly central memory T cell (TCM cell) phenotype. We present a bicistronic retroviral vector encoding both a tumor vasculature-targeted CAR and murine interleukin-15 (mIL-15), conferring enhanced effector functions, engraftment, tumor control, and TME reprogramming, including NK cell activation and reduced presence of M2 macrophages. The 4G-CAR-T cells coexpressing mIL-15 were further characterized by up-regulation of the antiapoptotic marker Bcl-2 and lower cell-surface expression of the inhibitory receptor PD-1. Overall, this work introduces robust tools for the development and evaluation of 4G-CAR-T cells in immunocompetent mice, an important step toward the acceleration of effective therapies reaching the clinic.

Indexed as

AnimalsCell LineCell Line, TumorFemaleGenetic EngineeringGenetic VectorsHumansImmunologic MemoryImmunotherapy, AdoptiveInterleukin-15Killer Cells, NaturalLymphocyte ActivationMiceMice, Inbred C57BLReceptors, Antigen, T-CellReceptors, Chimeric AntigenIL15 protein, humanInterleukin-15Receptors, Antigen, T-CellReceptors, Chimeric Antigen

Identifiers

PMID33156338
PMCPMC7653685
OpenAlexW3097472706

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.