Evidence map›Paper›PMID 35711141›Full record

ArticleMolecular therapy : the journal of the American Society of Gene Therapy2022

Universal allogeneic CAR T cells engineered with Sleeping Beauty transposons and CRISPR-CAS9 for cancer immunotherapy.

Jaitip Tipanee, Ermira Samara-Kuko, Thierry Gevaert, Marinee K Chuah, Thierry VandenDriessche

Open access · bronzeAbstract read
In one paragraph

Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 49 papers.

0numbers the graph read from it
0cells of the map it votes in
49citing papers in PubMed
7.1field-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

49 citing papers in PubMed, 71 citations in OpenAlex.

  1. Review
  2. Review
  3. Review
  4. Article
  5. Review
  6. Article
  7. Review
  8. Review
  9. Review
  10. Review
  11. Article
  12. Review
  13. Review
  14. Review
  15. Review
  16. Review
  17. Article
  18. Managing allorejection in off-the-shelf CAR-engineered cell therapies.Molecular therapy : the journal of the American Society of Gene Therapy · 2025
    Review
  19. Article
  20. 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

5 authors at 1 institution in 1 country.

Jaitip TipaneeDepartment of Gene Therapy and Regenerative Medicine, Faculty of Medicine and Pharmacy, Vrije Universiteit Brussel, Building D, Room D365, Laarbeeklaan 103, 1090 Brussels, Belgium.
Ermira Samara-KukoDepartment of Gene Therapy and Regenerative Medicine, Faculty of Medicine and Pharmacy, Vrije Universiteit Brussel, Building D, Room D365, Laarbeeklaan 103, 1090 Brussels, Belgium.
Thierry GevaertDepartment of Radiotherapy, Oncology Centre University Hospital Brussels (Universitair Ziekenhuis (UZ) Brussel), Vrije Universiteit Brussel, Brussels, Belgium.
Marinee K ChuahDepartment of Gene Therapy and Regenerative Medicine, Faculty of Medicine and Pharmacy, Vrije Universiteit Brussel, Building D, Room D365, Laarbeeklaan 103, 1090 Brussels, Belgium; Center for Molecular and Vascular Biology, Department of Cardiovascular Sciences, University of Leuven, 3000 Leuven, Belgium. Electronic address: thierry.vandendriessche@vub.be.
Thierry VandenDriesscheDepartment of Gene Therapy and Regenerative Medicine, Faculty of Medicine and Pharmacy, Vrije Universiteit Brussel, Building D, Room D365, Laarbeeklaan 103, 1090 Brussels, Belgium; Center for Molecular and Vascular Biology, Department of Cardiovascular Sciences, University of Leuven, 3000 Leuven, Belgium. Electronic address: marinee.chuah@vub.be.
Vrije Universiteit Brussel · BE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Allogeneic CD19-specific chimeric antigen receptor (CAR) T cells with inactivated donor T cell receptor (TCR) expression can be used as an "off-the-shelf" therapeutic modality for lymphoid malignancies, thus offering an attractive alternative to autologous, patient-derived T cells. Current approaches for T cell engineering mainly rely on the use of viral vectors. Here, we optimized and validated a non-viral genetic modification platform based on Sleeping Beauty (SB) transposons delivered with minicircles to express CD19-28z.CAR and CRISPR-Cas9 ribonucleoparticles to inactivate allogeneic TCRs. Efficient TCR gene disruption was achieved with minimal cytotoxicity and with attainment of robust and stable CD19-28z.CAR expression. The CAR T cells were responsive to CD19+ tumor cells with antitumor activities that induced complete tumor remission in NALM6 tumor-bearing mice while significantly reducing TCR alloreactivity and GvHD development. Single CAR signaling induced the similar T cell signaling signatures in TCR-disrupted CAR T cells and control CAR T cells. In contrast, TCR disruption inhibited T cell signaling/protein phosphorylation compared with the control CAR T cells during dual CAR/TCR signaling. This non-viral SB transposon-CRISPR-Cas9 combination strategy serves as an alternative for generating next-generation CD19-specific CAR T while reducing GvHD risk and easing potential manufacturing constraints intrinsic to viral vectors.

Indexed as

Graft vs Host DiseaseHematopoietic Stem Cell TransplantationNeoplasmsReceptors, Chimeric AntigenAnimalsAntigens, CD19CRISPR-Cas SystemsImmunotherapyImmunotherapy, AdoptiveMiceReceptors, Antigen, T-CellT-LymphocytesAntigens, CD19Receptors, Antigen, T-CellReceptors, Chimeric Antigenchimeric antigen receptorCRISPR-Cas9leukemiaSleeping BeautyT cell receptortransposon

Identifiers

PMID35711141
PMCPMC9552804
OpenAlexW4282965443

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
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.