ArticleTranslational oncology2023
Bicistronic CAR-T cells targeting CD123 and CLL1 for AML to reduce the risk of antigen escape.
Article in Translational oncology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 20 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
- Application and challenges of chimeric antigen receptor T cell therapy in the treatment of acute myeloid leukemia (Review).Oncology letters · 2026Review
- Solid tumour CAR-T cells engineered with fusion proteins targeting PD-L1 for localized IL-12 delivery.Nature biomedical engineering · 2026Article
- From monoclonals to bispecific T cell engagers: the evolving antibody-based therapy landscape in acute myeloid leukemia.Frontiers in immunology · 2026Review
- Review
- Hotspots evolution and frontiers of immunotherapy for the treatment of acute myeloid leukemia: A bibliometric analysis.Human vaccines & immunotherapeutics · 2025Article
- Emerging strategies in CAR-T cell therapy for acute myeloid leukemia: overcoming heterogeneity and improving safety through dual-antigen targeting.Experimental hematology & oncology · 2025Review
- Strategic innovations: Tackling challenges of immunotherapy in acute myeloid leukemia.Chinese journal of cancer research = Chung-kuo yen cheng yen chiu · 2025Article
- Targeting cancer stem cells with CAR-based immunotherapy: biology, evidence, and future directions.Cancer cell international · 2025Review
- Unveiling the potential of CLL-1: a promising target for AML therapy.Biomarker research · 2025Review
- Recent advances of CAR-T cells in acute myeloid leukemia.Therapeutic advances in hematology · 2025Review
- Review
- Review
- Recent Advances in Immune-Based Therapies for Acute Myeloid Leukemia.Blood cancer discovery · 2024Review
- A structural, genetic and clinical comparison of CAR-T cells and CAR-NK cells: companions or competitors?Frontiers in immunology · 2024Review
- Recent advances in CAR-T therapy for the treatment of acute myeloid leukemia.Therapeutic advances in hematology · 2024Review
- Bringing cell therapy to tumors: considerations for optimal CAR binder design.Antibody therapeutics · 2023Review
Corrections and comments
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Authors and funding
9 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
purposeAcute myeloid leukemia (AML) is a highly heterogeneous neoplastic disease with a poor prognosis that relapses even after its treatment with chimeric antigen receptor (CAR)-T cells targeting a single antigen. CD123 and CLL1 are expressed in most AML blasts and leukemia stem cells, and their low expression in normal hematopoietic stem cells makes them ideal targets for CAR-T. In this study, we tested the hypothesis that a new bicistronic CAR targeting CD123 and CLL1 can enhance antigenic coverage and prevent antigen escape and subsequent recurrence of AML.
methodsCD123 and CLL1 expressions were evaluated on AML cell lines and blasts. Then, in addition to concentrating on CD123 and CLL1, we introduced the marker/suicide gene RQR8 with a bicistronic CAR. Xenograft models of disseminated AML and in vitro coculture models were used to assess the anti-leukemia efficacy of CAR-T cells. The hematopoietic toxicity of CAR-T cells was evaluated in vitro by colony cell formation assays. It was demonstrated in vitro that the combination of rituximab and NK cells caused RQR8-mediated clearance of 123CL CAR-T cells.
resultsWe have successfully established bicistronic 123CL CAR-T cells that can target CD123 and CLL1. 123CL CAR-T cells effectively cleared AML cell lines and blasts. They also demonstrated appreciable anti-AML activity in animal transplant models. Moreover, 123CL CAR-T cells can be eliminated in an emergency by a natural safety switch and don't target hematopoietic stem cells.
conclusionsThe bicistronic CAR-T cells targeting CD123 and CLL1 may be a useful and secure method for treating AML.
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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.