ArticleJournal for immunotherapy of cancer2020
41BB-based and CD28-based CD123-redirected T-cells ablate human normal hematopoiesis in vivo.
Article in Journal for immunotherapy of cancer, 2020. 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 51 papers.
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Who cites it
51 citing papers in PubMed, 65 citations in OpenAlex.
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- 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
- Next-generation CAR-T therapy for acute myeloid leukemia: bridging innovation with clinical translation.Annals of hematology · 2026Review
- Immunological barriers and engineering strategies for CAR-T cell therapy in acute myeloid leukemia.Frontiers in immunology · 2026Review
- A novel chimeric antigen receptor T-cell therapy targeting CD84 for the treatment of acute myeloid and T-cell lymphoblastic leukemias.Leukemia · 2025Article
- The bispecific innate cell engager AFM28 eliminates CD123Nature communications · 2025Article
- CAR-T cell therapy for cancer: current challenges and future directions.Signal transduction and targeted therapy · 2025Review
- Surface downmodulation of TIM3 safeguards healthy cells but not acute myeloid leukemia from CAR T-cell therapy.HemaSphere · 2025Article
- Article
- Optimal Chimeric Antigen Receptor (CAR)-mRNA for Transient CAR T Cell Generation.International journal of molecular sciences · 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
- Recent advances of chimeric antigen receptor T-cell therapy for acute myeloid leukemia.Frontiers in immunology · 2025Review
- In-depth analysis of the safety of CAR-T cell therapy for solid tumors.Frontiers in immunology · 2025Review
- Anti-CD19 CAR-T cell therapy in relapsed/refractory t(8;21) acute myeloid leukemia with aberrant CD19 expression.Frontiers in immunology · 2025Article
- Loop33 × 123 CAR-T targeting CD33 and CD123 against immune escape in acute myeloid leukemia.Cancer immunology, immunotherapy : CII · 2024Article
- NSGS mice humanized with cord blood mononuclear cells show sustained and functional myeloid-lymphoid representation with limited graft-versus-host disease.Journal for immunotherapy of cancer · 2024Article
- CAR T-cell therapy in acute myeloid leukemia.Saudi medical journal · 2024Review
- Targeting the membrane-proximal C2-set domain of CD33 for improved CAR T cell therapy.Molecular therapy. Oncology · 2024Article
- Application of omics in the diagnosis, prognosis, and treatment of acute myeloid leukemia.Biomarker research · 2024Review
- Inhibitory CARs fail to protect from immediate T cell cytotoxicity.Molecular therapy : the journal of the American Society of Gene Therapy · 2024Article
Corrections and comments
- Erratum issued
Authors and funding
25 authors at 10 institutions in 8 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundAcute myeloid leukemia (AML) is a hematopoietic malignancy which is biologically, phenotypically and genetically very heterogeneous. Outcome of patients with AML remains dismal, highlighting the need for improved, less toxic therapies. Chimeric antigen receptor T-cell (CART) immunotherapies for patients with refractory or relapse (R/R) AML are challenging because of the absence of a universal pan-AML target antigen and the shared expression of target antigens with normal hematopoietic stem/progenitor cells (HSPCs), which may lead to life-threating on-target/off-tumor cytotoxicity. CD33-redirected and CD123-redirected CARTs for AML are in advanced preclinical and clinical development, and they exhibit robust antileukemic activity. However, preclinical and clinical controversy exists on whether such CARTs are myeloablative.
methodsWe set out to comparatively characterize in vitro and in vivo the efficacy and safety of 41BB-based and CD28-based CARCD123. We analyzed 97 diagnostic and relapse AML primary samples to investigate whether CD123 is a suitable immunotherapeutic target, and we used several xenograft models and in vitro assays to assess the myeloablative potential of our second-generation CD123 CARTs.
resultsHere, we show that CD123 represents a bona fide target for AML and show that both 41BB-based and CD28-based CD123 CARTs are very efficient in eliminating both AML cell lines and primary cells in vitro and in vivo. However, both 41BB-based and CD28-based CD123 CARTs ablate normal human hematopoiesis and prevent the establishment of de novo hematopoietic reconstitution by targeting both immature and myeloid HSPCs.
conclusionsThis study calls for caution when clinically implementing CD123 CARTs, encouraging its preferential use as a bridge to allo-HSCT in patients with R/R AML.
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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.