Evidence map›Paper›PMID 37173386›Full record

ArticleGene therapy2023

RapaCaspase-9-based suicide gene applied to the safety of IL-1RAP CAR-T cells.

Lucie Bouquet, Elodie Bôle-Richard, Walid Warda, Mathieu Neto Da Rocha, Rim Trad, Clémentine Nicod, Rafik Haderbache, Delphine Genin, Christophe Ferrand, Marina Deschamps

Erratum issuedOpen access · hybridAbstract read
In one paragraph

Article in Gene therapy, 2023. 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 22 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
22citing papers in PubMed, 1 pooled it
7.8field-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

22 citing papers in PubMed, 1 synthesis or guideline pooled it, 34 citations in OpenAlex.

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  8. Small-molecule control of CAR T cells.Nature reviews. Chemistry · 2025
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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

10 authors at 1 institution in 2 countries.

Lucie BouquetUniv. Bourgogne Franche-Comté, INSERM, EFS BFC, UMR1098, RIGHT Interactions Greffon-Hôte-Tumeur/Ingénierie Cellulaire et Génique, F-25 000, Besançon, France.
Elodie Bôle-RichardUniv. Bourgogne Franche-Comté, INSERM, EFS BFC, UMR1098, RIGHT Interactions Greffon-Hôte-Tumeur/Ingénierie Cellulaire et Génique, F-25 000, Besançon, France.
Walid WardaCanCell Therapeutics, 25 000, Besançon, France.
Mathieu Neto Da RochaCanCell Therapeutics, 25 000, Besançon, France.
Rim TradUniv. Bourgogne Franche-Comté, INSERM, EFS BFC, UMR1098, RIGHT Interactions Greffon-Hôte-Tumeur/Ingénierie Cellulaire et Génique, F-25 000, Besançon, France.
Clémentine NicodUniv. Bourgogne Franche-Comté, INSERM, EFS BFC, UMR1098, RIGHT Interactions Greffon-Hôte-Tumeur/Ingénierie Cellulaire et Génique, F-25 000, Besançon, France.
Rafik HaderbacheUniv. Bourgogne Franche-Comté, INSERM, EFS BFC, UMR1098, RIGHT Interactions Greffon-Hôte-Tumeur/Ingénierie Cellulaire et Génique, F-25 000, Besançon, France.
Delphine GeninUniv. Bourgogne Franche-Comté, INSERM, EFS BFC, UMR1098, RIGHT Interactions Greffon-Hôte-Tumeur/Ingénierie Cellulaire et Génique, F-25 000, Besançon, France.
Christophe FerrandUniv. Bourgogne Franche-Comté, INSERM, EFS BFC, UMR1098, RIGHT Interactions Greffon-Hôte-Tumeur/Ingénierie Cellulaire et Génique, F-25 000, Besançon, France.ORCID http://orcid.org/0000-0003-0119-3919
Marina DeschampsUniv. Bourgogne Franche-Comté, INSERM, EFS BFC, UMR1098, RIGHT Interactions Greffon-Hôte-Tumeur/Ingénierie Cellulaire et Génique, F-25 000, Besançon, France. marina.deschamps@efs.sante.fr.ORCID http://orcid.org/0000-0002-0564-0926
Inserm · FR

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Even if adoptive cell transfer (ACT) has already shown great clinical efficiency in different types of disease, such as cancer, some adverse events consistently occur, and suicide genes are an interesting system to manage these events. Our team developed a new medical drug candidate, a chimeric antigen receptor (CAR) targeting interleukin-1 receptor accessory protein (IL-1RAP), which needs to be evaluated in clinical trials with a clinically applicable suicide gene system. To prevent side effects and ensure the safety of our candidate, we devised two constructs carrying an inducible suicide gene, RapaCasp9-G or RapaCasp9-A, containing a single-nucleotide polymorphism (rs1052576) affecting the efficiency of endogenous caspase 9. These suicide genes are activated by rapamycin and based on the fusion of human caspase 9 with a modified human FK-binding protein, allowing conditional dimerization. RapaCasp9-G- and RapaCasp9-A-expressing gene-modified T cells (GMTCs) were produced from healthy donors (HDs) and acute myeloid leukemia (AML) donors. The RapaCasp9-G suicide gene demonstrated better efficiency, and we showed its in vitro functionality in different clinically relevant culture conditions. Moreover, as rapamycin is not pharmacologically inert, we also demonstrated its safe use as part of our therapy.

Indexed as

Immunotherapy, AdoptiveInterleukin-1 Receptor Accessory ProteinCaspase 9HumansSirolimusT-LymphocytesCaspase 9Interleukin-1 Receptor Accessory ProteinSirolimus

Identifiers

PMID37173386
PMCPMC10506905
OpenAlexW4376279108

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

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.