Evidence map›Paper›PMID 38266153›Full record

ArticleBlood advances2024

Dual-targeting CD33/CD123 NANOBODY T-cell engager with potent anti-AML activity and good safety profile.

Zhihong Zeng, Annelies Roobrouck, Geert Deschamps, Helene Bonnevaux, Stephane Guerif, Veronique De Brabandere, Céline Amara, Eline Dejonckheere, Angela Virone-Oddos, Marielle Chiron and 2 more

Abstract read
In one paragraph

Article in Blood advances, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.

0numbers the graph read from it
0cells of the map it votes in
21citing 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

21 citing papers in PubMed.

  1. T-cell Receptor (TCR) Targeting with Multivalent T-cell Engagers.bioRxiv : the preprint server for biology · 2026
    Article
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  10. Antigen-directed p53 restoration inFrontiers in oncology · 2026
    Article
  11. Review
  12. Review
  13. Review
  14. Advances in Nanobody-Based Platforms for Precision Cancer Diagnosis and Therapy.Polymer science & technology (Washington, D.C.) · 2025
    Review
  15. Review
  16. Review
  17. Article
  18. Article
  19. Review
  20. Engaging T cells for cleanup.Frontiers in immunology · 2025
    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.

Zhihong ZengDepartment of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX.
Annelies RoobrouckSanofi, R&D, Ghent, Belgium.
Geert DeschampsSanofi, R&D, Ghent, Belgium.
Helene BonnevauxSanofi, R&D, Vitry-sur-Seine, France.
Stephane GuerifSanofi, R&D, Vitry-sur-Seine, France.
Veronique De BrabandereSanofi, R&D, Ghent, Belgium.
Céline AmaraSanofi, R&D, Vitry-sur-Seine, France.
Eline DejonckheereSanofi, R&D, Ghent, Belgium.
Angela Virone-OddosSanofi, R&D, Vitry-sur-Seine, France.
Marielle ChironSanofi, R&D, Vitry-sur-Seine, France.ORCID 0000-0003-0798-7066
Marina KonoplevaDepartment of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX.ORCID 0000-0002-9347-2212
Melissa DullaersSanofi, R&D, Ghent, Belgium.ORCID 0000-0003-0223-230X

Funding

Tumor Evolution and Metastasis ProgramP30CA016672 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI Fabien Delerue · 1985 to 2026
$290.8M
NCI NIH HHS P30 CA016672
6 · The paper itself

Abstract

abstractNovel therapies are needed for effective treatment of acute myeloid leukemia (AML). Relapse is common and salvage treatment with cytotoxic chemotherapy is rarely curative. CD123 and CD33, 2 clinically validated targets in AML, are jointly expressed on blasts and leukemic stem cells in >95% of patients with AML. However, their expression is heterogenous between subclones and between patients, which may affect the efficacy of single-targeting agents in certain patient populations. We present here a dual-targeting CD33/CD123 NANOBODY T-cell engager (CD33/CD123-TCE) that was designed to decrease the risk of relapse from possible single antigen-negative clones and to increase coverage within and across patients. CD33/CD123-TCE killed AML tumor cells expressing 1 or both antigens in vitro. Compared with single-targeting control compounds, CD33/CD123-TCE conferred equal or better ex vivo killing of AML blasts in most primary AML samples tested, suggesting a broader effectiveness across patients. In a disseminated cell-line-derived xenograft mouse model of AML, CD33/CD123-TCE cleared cancer cells in long bones and in soft tissues. As cytokine release syndrome is a well-documented adverse effect of TCE, the compound was tested in a cytokine release assay and shown to induce less cytokines compared to a CD123 single-targeting control. In an exploratory single-dose nonhuman primate study, CD33/CD123-TCE revealed a favorable PK profile. Depletion of CD123 and CD33 expressing cells was observed, but there were neither signs of cytokine release syndrome nor clinical signs of toxicity. Taken together, the CD33/CD123 dual-targeting NANOBODY TCE exhibits potent and safe anti-AML activity and promises a broad patient coverage.

Indexed as

Interleukin-3 Receptor alpha SubunitLeukemia, Myeloid, AcuteSialic Acid Binding Ig-like Lectin 3Single-Domain AntibodiesAnimalsCell Line, TumorFemaleHumansMiceT-LymphocytesXenograft Model Antitumor AssaysInterleukin-3 Receptor alpha SubunitSialic Acid Binding Ig-like Lectin 3Single-Domain Antibodies

Identifiers

PMID38266153
PMCPMC11063226

What OpenQuestion holds

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LicenceCC BY-NC-ND
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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.