ArticleBlood2024
A dual-receptor T-cell platform with Ab-TCR and costimulatory receptor achieves specificity and potency against AML.
Article in Blood, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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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
21 citing papers in PubMed, 24 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
- Trispecific targeting of T cells engineered with TCR mimic antibodies to limit antigen escape.Journal for immunotherapy of cancer · 2026Article
- Immunological barriers and engineering strategies for CAR-T cell therapy in acute myeloid leukemia.Frontiers in immunology · 2026Review
- Computational Design of a TCR-like Human VComputational and structural biotechnology journal · 2026Article
- Targeting the roots of myeloid malignancies with T cell receptors.Nature reviews. Cancer · 2025Review
- Emerging strategies in CAR-T cell therapy for acute myeloid leukemia: overcoming heterogeneity and improving safety through dual-antigen targeting.Experimental hematology & oncology · 2025Review
- Disrupting the balance between activating and inhibitory receptors of γδT cells for effective cancer immunotherapy.Nature reviews. Cancer · 2025Review
- Transitioning from native to synthetic receptors: broadening T-cell engineering and beyond.Cellular & molecular immunology · 2025Review
- Concept CARs are picking up speed.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Review
- Novel strategies to manage CAR-T cell toxicity.Nature reviews. Drug discovery · 2025Review
- From molecular design to clinical translation: dual-targeted CAR-T strategies in cancer immunotherapy.International journal of biological sciences · 2025Review
- Recent advances of chimeric antigen receptor T-cell therapy for acute myeloid leukemia.Frontiers in immunology · 2025Review
- The Wilms' Tumor Suppressor WT1 in Cardiomyocytes: Implications for Cardiac Homeostasis and Repair.Cells · 2024Review
- Evolving strategies for addressing CAR T-cell toxicities.Cancer metastasis reviews · 2024Review
- Article
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- The Potential of Siglecs and Sialic Acids as Biomarkers and Therapeutic Targets in Tumor Immunotherapy.Cancers · 2024Review
- Finding potential targets in cell-based immunotherapy for handling the challenges of acute myeloid leukemia.Frontiers in immunology · 2024Review
- Molecular mechanisms of Y chromosome loss andFuture science OA · 2024Article
- Challenges and innovations in CAR-T cell therapy: a comprehensive analysis.Frontiers in oncology · 2024Review
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Authors and funding
19 authors at 2 institutions in 1 country.
Funding
Abstract
abstractChimeric antigen receptor T-cell (CAR T) therapy has produced remarkable clinical responses in B-cell neoplasms. However, many challenges limit this class of agents for the treatment of other cancer types, in particular the lack of tumor-selective antigens for solid tumors and other hematological malignancies, such as acute myeloid leukemia (AML), which may be addressed without significant risk of severe toxicities while providing sufficient abundance for efficient tumor suppression. One approach to overcome this hurdle is dual targeting by an antibody-T-cell receptor (AbTCR) and a chimeric costimulatory signaling receptor (CSR) to 2 different antigens, in which both antigens are found together on the cancer cells but not together on normal cells. To explore this proof of concept in AML, we engineered a new T-cell format targeting Wilms tumor 1 protein (WT1) and CD33; both are highly expressed on most AML cells. Using an AbTCR comprising a newly developed TCR-mimic monoclonal antibody against the WT1 RMFPNAPYL (RMF) epitope/HLA-A2 complex, ESK2, and a secondary CSR comprising a single-chain variable fragment directed to CD33 linked to a truncated CD28 costimulatory fragment, this unique platform confers specific T-cell cytotoxicity to the AML cells while sparing healthy hematopoietic cells, including CD33+ myelomonocytic normal cells. These data suggest that this new platform, named AbTCR-CSR, through the combination of a AbTCR CAR and CSR could be an effective strategy to reduce toxicity and improve specificity and clinical outcomes in adoptive T-cell therapy in 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.