Evidence map›Paper›PMID 39564539›Full record

ArticleHemaSphere2024

A single-chain variable fragment-based bispecific T-cell activating antibody against CD117 enables T-cell mediated lysis of acute myeloid leukemia and hematopoietic stem and progenitor cells.

Laura Volta, Renier Myburgh, Mara Hofstetter, Christian Koch, Jonathan D Kiefer, Celeste Gobbi, Francesco Manfredi, Kathrin Zimmermann, Philipp Kaufmann, Serena Fazio and 15 more

Abstract read
In one paragraph

Article in HemaSphere, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.

0numbers the graph read from it
0cells of the map it votes in
9citing papers in PubMed
–field-weighted citation impact
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

9 citing papers in PubMed.

  1. Article
  2. Review
  3. Article
  4. Article
  5. Article
  6. Review
  7. Targeting CD117 on hematopoietic stem and progenitor cells impairs CAR T cell activity.Molecular therapy : the journal of the American Society of Gene Therapy · 2025
    Article
  8. Article
  9. Article
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

25 authors.

Laura VoltaDepartment of Medical Oncology and Hematology University and University Hospital Zürich Zürich Switzerland.
Renier MyburghDepartment of Medical Oncology and Hematology University and University Hospital Zürich Zürich Switzerland.
Mara HofstetterDepartment of Medical Oncology and Hematology University and University Hospital Zürich Zürich Switzerland.
Christian KochDepartment of Medical Oncology and Hematology University and University Hospital Zürich Zürich Switzerland.
Jonathan D KieferDepartment of Chemistry and Applied Biosciences, Institute of Pharmaceutical Sciences Swiss Federal Institute of Technology (ETH Zürich) Zürich Switzerland.
Celeste GobbiDepartment of Medical Oncology and Hematology University and University Hospital Zürich Zürich Switzerland.
Francesco ManfrediDepartment of Medical Oncology and Hematology University and University Hospital Zürich Zürich Switzerland.
Kathrin ZimmermannDepartment of Medical Oncology and Hematology University and University Hospital Zürich Zürich Switzerland.
Philipp KaufmannDepartment of Medical Oncology and Hematology University and University Hospital Zürich Zürich Switzerland.
Serena FazioDepartment of Medical Oncology and Hematology University and University Hospital Zürich Zürich Switzerland.
Christian PellegrinoDepartment of Medical Oncology and Hematology University and University Hospital Zürich Zürich Switzerland.
Norman F RusskampDepartment of Medical Oncology and Hematology University and University Hospital Zürich Zürich Switzerland.
Danielle VillarsPhire/ATLyphe, Wyss Zurich Translational Center ETH Zürich/University of Zürich Zürich Switzerland.
Mattia MatasciPhilochem AG Otelfingen Switzerland.
Monique MaurerDepartment of Medical Oncology and Hematology University and University Hospital Zürich Zürich Switzerland.
Jan MuellerDepartment of Medical Oncology and Hematology University and University Hospital Zürich Zürich Switzerland.
Florin SchneiterDepartment of Biosystems Science and Engineering ETH Zurich Basel Switzerland.
Paul BüschlDepartment of Medical Oncology and Hematology University and University Hospital Zürich Zürich Switzerland.
Niclas HarrerDepartment of Medical Oncology and Hematology University and University Hospital Zürich Zürich Switzerland.
Jacqueline MockDepartment of Chemistry and Applied Biosciences, Institute of Pharmaceutical Sciences Swiss Federal Institute of Technology (ETH Zürich) Zürich Switzerland.
Stefan BalabanovDepartment of Medical Oncology and Hematology University and University Hospital Zürich Zürich Switzerland.
César Nombela-ArrietaDepartment of Medical Oncology and Hematology University and University Hospital Zürich Zürich Switzerland.ORCID https://orcid.org/0000-0003-0415-259X
Timm SchroederDepartment of Biosystems Science and Engineering ETH Zurich Basel Switzerland.
Dario NeriDepartment of Chemistry and Applied Biosciences, Institute of Pharmaceutical Sciences Swiss Federal Institute of Technology (ETH Zürich) Zürich Switzerland.
Markus G ManzDepartment of Medical Oncology and Hematology University and University Hospital Zürich Zürich Switzerland.ORCID https://orcid.org/0000-0002-4676-7931

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Acute myeloid leukemia (AML) derives from hematopoietic stem and progenitor cells (HSPCs). To date, no AML-exclusive, non-HSPC-expressed cell-surface target molecules for AML selective immunotherapy have been identified. Therefore, to still apply surface-directed immunotherapy in this disease setting, time-limited combined immune-targeting of AML cells and healthy HSPCs, followed by hematopoietic stem cell transplantation (HSCT), might be a viable therapeutic approach. To explore this, we generated a recombinant single-chain variable fragment-based bispecific T-cell engaging and activating antibody directed against CD3 on T-cells and CD117, the surface receptor for stem cell factor, expressed by both AML cells and healthy HSPCs. Bispecific CD117xCD3 targeting induced lysis of CD117-positive healthy human HSPCs, AML cell lines and patient-derived AML blasts in the presence of T-cells at subnanomolar concentrations in vitro. Furthermore, in immunocompromised mice, engrafted with human CD117-expressing leukemia cells and human T-cells, the bispecific molecule efficiently prevented leukemia growth in vivo. Additionally, in immunodeficient mice transplanted with healthy human HSPCs, the molecule decreased the number of CD117-positive cells in vivo. Therefore, bispecific CD117xCD3 targeting might be developed clinically in order to reduce CD117-expressing leukemia cells and HSPCs prior to HSCT.

Identifiers

PMID39564539
PMCPMC11574467

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Registered trials

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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.