ArticleBlood advances2023
IL-3-zetakine combined with a CD33 costimulatory receptor as a dual CAR approach for safer and selective targeting of AML.
Article in Blood advances, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed, 32 citations in OpenAlex.
- Preclinical advances and mechanistic insights of CAR-T therapy for acute myeloid leukemia: from target iteration to microenvironment regulation.Annals of medicine · 2026Review
- Two Decades ofCancers · 2026Review
- Nanobody-Engineered CLL-1 CAR T Cells: Optimizing Tumor-Specific Cytotoxicity and Minimizing Off-Tumor Toxicity.Cancer research communications · 2026Article
- Review
- Emerging strategies in CAR-T cell therapy for acute myeloid leukemia: overcoming heterogeneity and improving safety through dual-antigen targeting.Experimental hematology & oncology · 2025Review
- Advancing CIK cell immunotherapy: highlights from the second international conference on DC-CIK and CAR-CIK approaches.Cancer immunology, immunotherapy : CII · 2025Article
- Targeting cancer stem cells with CAR-based immunotherapy: biology, evidence, and future directions.Cancer cell international · 2025Review
- CAR-T cells targeting CCR9 and CD1a for the treatment of T cell acute lymphoblastic leukemia.Journal of hematology & oncology · 2025Article
- Review
- Optimized GMP-grade production of non-viral Sleeping Beauty-generated CARCIK cells for enhanced fitness and clinical scalability.Journal of translational medicine · 2025Article
- Expanding the CAR toolbox with high throughput screening strategies for CAR domain exploration: a comprehensive review.Journal for immunotherapy of cancer · 2025Review
- Cytokine-Induced Killer Cells: A Unique Platform for Adoptive Cell Immunotherapy after Allogeneic Hematopoietic Stem Cell Transplantation.Transfusion medicine and hemotherapy : offizielles Organ der Deutschen Gesellschaft fur Transfusionsmedizin und Immunhamatologie · 2025Review
- Review
- Recent advances of chimeric antigen receptor T-cell therapy for acute myeloid leukemia.Frontiers in immunology · 2025Review
- From molecular design to clinical translation: dual-targeted CAR-T strategies in cancer immunotherapy.International journal of biological sciences · 2025Review
- Advancing Chimeric Antigen Receptor T-Cell Therapy for Acute Myeloid Leukemia: Current Limitations and Emerging Strategies.Pharmaceuticals (Basel, Switzerland) · 2024Review
- The development and application of chimeric antigen receptor natural killer (CAR-NK) cells for cancer therapy: current state, challenges and emerging therapeutic advances.Experimental hematology & oncology · 2024Review
- Significant Advancements and Evolutions in Chimeric Antigen Receptor Design.International journal of molecular sciences · 2024Review
- T cell-redirecting therapies in hematological malignancies: Current developments and novel strategies for improved targeting.Molecular therapy : the journal of the American Society of Gene Therapy · 2024Review
- Artificial Intelligence-Powered Molecular Docking and Steered Molecular Dynamics for Accurate scFv Selection of Anti-CD30 Chimeric Antigen Receptors.International journal of molecular sciences · 2024Article
Corrections and comments
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Authors and funding
22 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Acute myeloid leukemia (AML) still represents an unmet clinical need for adult and pediatric patients. Adoptive cell therapy by chimeric antigen receptor (CAR)-engineered T cells demonstrated a high therapeutic potential, but further development is required to ensure a safe and durable disease remission in AML, especially in elderly patients. To date, translation of CAR T-cell therapy in AML is limited by the absence of an ideal tumor-specific antigen. CD123 and CD33 are the 2 most widely overexpressed leukemic stem cell biomarkers but their shared expression with endothelial and hematopoietic stem and progenitor cells increases the risk of undesired vascular and hematologic toxicities. To counteract this issue, we established a balanced dual-CAR strategy aimed at reducing off-target toxicities while retaining full functionality against AML. Cytokine-induced killer (CIK) cells, coexpressing a first-generation low affinity anti-CD123 interleukin-3-zetakine (IL-3z) and an anti-CD33 as costimulatory receptor without activation signaling domains (CD33.CCR), demonstrated a powerful antitumor efficacy against AML targets without any relevant toxicity on hematopoietic stem and progenitor cells and endothelial cells. The proposed optimized dual-CAR cytokine-induced killer cell strategy could offer the opportunity to unleash the potential of specifically targeting CD123+/CD33+ leukemic cells while minimizing toxicity against healthy cells.
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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.