Evidence map›Paper›PMID 36428578›Full record

ArticleCancers2022

T Cells Directed against the Metastatic Driver Chondromodulin-1 in Ewing Sarcoma: Comparative Engineering with CRISPR/Cas9 vs. Retroviral Gene Transfer for Adoptive Transfer.

Busheng Xue, Kristina von Heyking, Hendrik Gassmann, Mansour Poorebrahim, Melanie Thiede, Kilian Schober, Josef Mautner, Julia Hauer, Jürgen Ruland, Dirk H Busch and 2 more

Open access · goldAbstract read
In one paragraph

Article in Cancers, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
0.2field-weighted citation impact, top 44% 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

1 citing paper in PubMed, 2 citations in OpenAlex.

  1. 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

12 authors at 6 institutions in 2 countries.

Busheng XueDepartment of Pediatrics, Children's Cancer Research Center, Kinderklinik München Schwabing, School of Medicine, Technical University of Munich, 80804 Munich, Germany.ORCID 0000-0002-7436-6588
Kristina von HeykingDepartment of Pediatrics, Children's Cancer Research Center, Kinderklinik München Schwabing, School of Medicine, Technical University of Munich, 80804 Munich, Germany.
Hendrik GassmannDepartment of Pediatrics, Children's Cancer Research Center, Kinderklinik München Schwabing, School of Medicine, Technical University of Munich, 80804 Munich, Germany.ORCID 0000-0003-2503-4912
Mansour PoorebrahimDepartment of Pediatrics, Children's Cancer Research Center, Kinderklinik München Schwabing, School of Medicine, Technical University of Munich, 80804 Munich, Germany.
Melanie ThiedeDepartment of Pediatrics, Children's Cancer Research Center, Kinderklinik München Schwabing, School of Medicine, Technical University of Munich, 80804 Munich, Germany.
Kilian SchoberInstitute for Medical Microbiology, Immunology and Hygiene, School of Medicine, Technical University of Munich, 81674 Munich, Germany.
Josef MautnerDepartment of Gene Vectors, Helmholtz Centre Munich, 81377 Munich, Germany.
Julia HauerDepartment of Pediatrics, Children's Cancer Research Center, Kinderklinik München Schwabing, School of Medicine, Technical University of Munich, 80804 Munich, Germany.ORCID 0000-0002-4058-3058
Jürgen RulandDZIF, German Center for Infection Research, Partner Site Munich, Germany Institute of Clinical, 81675 Munich, Germany.
Dirk H BuschInstitute for Medical Microbiology, Immunology and Hygiene, School of Medicine, Technical University of Munich, 81674 Munich, Germany.ORCID 0000-0001-8713-093X
Uwe ThielDepartment of Pediatrics, Children's Cancer Research Center, Kinderklinik München Schwabing, School of Medicine, Technical University of Munich, 80804 Munich, Germany.
Stefan E G BurdachDepartment of Pediatrics, Children's Cancer Research Center, Kinderklinik München Schwabing, School of Medicine, Technical University of Munich, 80804 Munich, Germany.
München Klinik Schwabing · DEGerman Cancer Research Center · DEGerman Center for Infection Research · DEHelmholtz Zentrum München · DEInstitute of Medical Microbiology and Hygiene · DEUniversity of British Columbia · CA

Funding

China Scholarship Council 201908210290Cura Placida Children's Cancer Research Foundation 06082021 and 5110378Deutsche Forschungsgemeinschaft 501830041'Du musst kämpfen' Wohltätigkeitsinitiative 200310stbGerman Federal Government BMBF XVIR-RIB-PEMSt. Baldrick's Foundation 663113
6 · The paper itself

Abstract

Ewing sarcoma (EwS) is a highly malignant sarcoma of bone and soft tissue with early metastatic spread and an age peak in early puberty. The prognosis in advanced stages is still dismal, and the long-term effects of established therapies are severe. Efficacious targeted therapies are urgently needed. Our previous work has provided preliminary safety and efficacy data utilizing T cell receptor (TCR) transgenic T cells, generated by retroviral gene transfer, targeting HLA-restricted peptides on the tumor cell derived from metastatic drivers. Here, we compared T cells engineered with either CRISPR/Cas9 or retroviral gene transfer. Firstly, we confirmed the feasibility of the orthotopic replacement of the endogenous TCR by CRISPR/Cas9 with a TCR targeting our canonical metastatic driver chondromodulin-1 (CHM1). CRISPR/Cas9-engineered T cell products specifically recognized and killed HLA-A*02:01+ EwS cell lines. The efficiency of retroviral transduction was higher compared to CRISPR/Cas9 gene editing. Both engineered T cell products specifically recognized tumor cells and elicited cytotoxicity, with CRISPR/Cas9 engineered T cells providing prolonged cytotoxic activity. In conclusion, T cells engineered with CRISPR/Cas9 could be feasible for immunotherapy of EwS and may have the advantage of more prolonged cytotoxic activity, as compared to T cells engineered with retroviral gene transfer.

Indexed as

chondromodulin-1CRISPR/Cas9Ewing sarcomaimmunotherapyorthotopic TCR replacementretroviral transduction

Identifiers

PMID36428578
PMCPMC9688113
OpenAlexW4308722894

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.