ArticleProceedings of the National Academy of Sciences of the United States of America2019
Gene-edited stem cells enable CD33-directed immune therapy for myeloid malignancies.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 83 papers.
What it found
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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.
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Who cites it
83 citing papers in PubMed, 129 citations in OpenAlex.
- CRISPR-Cas9 CD33-deleted allogeneic hematopoietic cell transplantation with gemtuzumab ozogamicin maintenance in AML: a phase 1/2 trial.Nature medicine · 2026Trial
- Editing around the target: epitope engineering to protect stem cell grafts.Blood advances · 2026Review
- CRISPR Genome Editing and the Future of Leukaemia Immunotherapy.Health science reports · 2026Article
- Engraftment Outcome of CRISPR/Cas9-Edited Hematopoietic Stem Cells for Genetic Diseases: A Systematic Review and Meta-Analysis of Preclinical Evidence.Journal of hematology · 2026Article
- CAR T cells derived from a novel, high-affinity anti-CLL-1 monoclonal antibody exhibit a significant anti-AML effect.Cancer immunology, immunotherapy : CII · 2026Article
- Emerging trends in gene and cell therapy: CRISPR in DNA editing and beyond.Cell reports. Medicine · 2026Review
- Antigen-directed p53 restoration inFrontiers in oncology · 2026Article
- Review
- Inhibiting ferroptosis enhances ex vivo expansion of human haematopoietic stem cells.Nature cell biology · 2025Article
- CAR-T cell therapy for cancer: current challenges and future directions.Signal transduction and targeted therapy · 2025Review
- CAR-T Cell Therapy for Acute Myeloid Leukemia: Where Do We Stand Now?Current oncology (Toronto, Ont.) · 2025Review
- Protection of CD33-modified hematopoietic stem cell progeny from CD33-directed CAR T cells in rhesus macaques.Blood advances · 2025Article
- Multiplex base editing to protect from CD33 directed drugs for immune and gene therapy.Nature communications · 2025Article
- Precision epitope editing: A path to advanced immunotherapies.Cell insight · 2025Review
- Human CD33 deficiency is associated with mild alteration of circulating white blood cell counts.PLoS genetics · 2025Article
- CD33-CD123 IF-THEN Gating Reduces Toxicity while Enhancing the Specificity and Memory Phenotype of AML-Targeting CAR-T Cells.Blood cancer discovery · 2025Article
- A review of common immunotherapy and nano immunotherapy for acute myeloid leukemia.Frontiers in immunology · 2025Review
- Improving efficacy of in vivo therapy of sickle cell disease by hijacking natural biology of hematopoietic stem cells.Molecular therapy : the journal of the American Society of Gene Therapy · 2024Article
- Leveraging CRISPR gene editing technology to optimize the efficacy, safety and accessibility of CAR T-cell therapy.Leukemia · 2024Review
- Review
23 more citing papers are in PubMed but not listed here.
Corrections and comments
- Erratum issued
Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
Antigen-directed immunotherapies for acute myeloid leukemia (AML), such as chimeric antigen receptor T cells (CAR-Ts) or antibody-drug conjugates (ADCs), are associated with severe toxicities due to the lack of unique targetable antigens that can distinguish leukemic cells from normal myeloid cells or myeloid progenitors. Here, we present an approach to treat AML by targeting the lineage-specific myeloid antigen CD33. Our approach combines CD33-targeted CAR-T cells, or the ADC Gemtuzumab Ozogamicin with the transplantation of hematopoietic stem cells that have been engineered to ablate CD33 expression using genomic engineering methods. We show highly efficient genetic ablation of CD33 antigen using CRISPR/Cas9 technology in human stem/progenitor cells (HSPC) and provide evidence that the deletion of CD33 in HSPC doesn't impair their ability to engraft and to repopulate a functional multilineage hematopoietic system in vivo. Whole-genome sequencing and RNA sequencing analysis revealed no detectable off-target mutagenesis and no loss of functional p53 pathways. Using a human AML cell line (HL-60), we modeled a postremission marrow with minimal residual disease and showed that the transplantation of CD33-ablated HSPCs with CD33-targeted immunotherapy leads to leukemia clearance, without myelosuppression, as demonstrated by the engraftment and recovery of multilineage descendants of CD33-ablated HSPCs. Our study thus contributes to the advancement of targeted immunotherapy and could be replicated in other malignancies.
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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.