ArticleJournal of hematology & oncology2022
Electrostatic anti-CD33-antibody-protamine nanocarriers as platform for a targeted treatment of acute myeloid leukemia.
Article in Journal of hematology & oncology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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.
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.
Who cites it
13 citing papers in PubMed, 22 citations in OpenAlex.
- Transport of cytotoxic cyanine dyes coupled to siRNA into hematopoietic cancer cells with CD20-, CD22- or CD33-targeting ELART nanocarriers.Scientific reports · 2026Article
- Article
- Advances in ligand-targeted nanodelivery systems for leukemia therapy: from single- to dual-ligand strategies.Journal of translational medicine · 2026Review
- Staufen dsRNA-binding domain as modules to design bifunctional antibodies for siRNA delivery.Nucleic acids research · 2026Article
- Recent advances in drug delivery and treatment strategies for acute myeloid leukemia.International journal of pharmaceutics · 2025Review
- Significance of targeting DNMT3A mutations in AML.Annals of hematology · 2025Review
- Advances in the application of patient-derived xenograft models in acute leukemia resistance.Cancer drug resistance (Alhambra, Calif.) · 2025Review
- Loop33 × 123 CAR-T targeting CD33 and CD123 against immune escape in acute myeloid leukemia.Cancer immunology, immunotherapy : CII · 2024Article
- Routes and molecular mechanisms of central nervous system involvement in acute myeloid leukemia (Review).Oncology reports · 2024Review
- Targeted therapy for leukemia based on nanomaterials.Heliyon · 2024Review
- An Overview of Nanoparticle-Based Delivery Platforms for mRNA Vaccines for Treating Cancer.Vaccines · 2024Review
- FLT3-Mutated Leukemic Stem Cells: Mechanisms of Resistance and New Therapeutic Targets.Cancers · 2024Review
- Biomimetic nanocarriers: integrating natural functions for advanced therapeutic applications.Beilstein journal of nanotechnology · 2024Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
27 authors at 6 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundAcute myeloid leukemia (AML) is a fatal clonal hematopoietic malignancy, which results from the accumulation of several genetic aberrations in myeloid progenitor cells, with a worldwide 5-year survival prognosis of about 30%. Therefore, the development of more effective therapeutics with novel mode of action is urgently demanded. One common mutated gene in the AML is the DNA-methyltransferase DNMT3A whose function in the development and maintenance of AML is still unclear. To specifically target "undruggable" oncogenes, we initially invented an RNAi-based targeted therapy option that uses the internalization capacity of a colorectal cancer specific anti-EGFR-antibody bound to cationic protamine and the anionic siRNA. Here, we present a new experimental platform technology of molecular oncogene targeting in AML.
methodsOur AML-targeting system consists of an internalizing anti-CD33-antibody-protamine conjugate, which together with anionic molecules such as siRNA or ibrutinib-Cy3.5 and cationic free protamine spontaneously assembles into vesicular nanocarriers in aqueous solution. These nanocarriers were analyzed concerning their physical properties and relevant characteristics in vitro in cell lines and in vivo in xenograft tumor models and patient-derived xenograft leukemia models with the aim to prepare them for translation into clinical application.
resultsThe nanocarriers formed depend on a balanced electrostatic combination of the positively charged cationic protamine-conjugated anti-CD33 antibody, unbound cationic protamine and the anionic cargo. This nanocarrier transports its cargo safely into the AML target cells and has therapeutic activity against AML in vitro and in vivo. siRNAs directed specifically against two common mutated genes in the AML, the DNA-methyltransferase DNMT3A and FLT3-ITD lead to a reduction of clonal growth in vitro in AML cell lines and inhibit tumor growth in vivo in xenotransplanted cell lines. Moreover, oncogene knockdown of DNMT3A leads to increased survival of mice carrying leukemia patient-derived xenografts. Furthermore, an anionic derivative of the approved Bruton's kinase (BTK) inhibitor ibrutinib, ibrutinib-Cy3.5, is also transported by this nanocarrier into AML cells and decreases colony formation.
conclusionsWe report important results toward innovative personalized, targeted treatment options via electrostatic nanocarrier therapy in AML.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
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.