ArticleJournal for immunotherapy of cancer2024
Developing a membrane-proximal CD33-targeting CAR T cell.
Article in Journal for immunotherapy of cancer, 2024. 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.
- Synergistic immune interactions between T cells and natural killer cells in allogeneic haematopoietic stem cell transplantation for acute myeloid leukaemia: current status and future directions.Annals of medicine · 2026Review
- Preclinical advances and mechanistic insights of CAR-T therapy for acute myeloid leukemia: from target iteration to microenvironment regulation.Annals of medicine · 2026Review
- A guide to CAR T cell therapies: development, current status and future prospects.Nature reviews. Immunology · 2026Review
- Humanized biparatopic nanobody-based CAR-T cells overcome antigen-heterogeneity in multiple myeloma.Journal of translational medicine · 2026Article
- The search for safe and effective CAR-T targets in AML.Blood cancer journal · 2026Review
- Sialic acids modulate immune responses in cancer: Therapeutic opportunities.The Journal of biological chemistry · 2026Review
- 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
- A framework integrating multiscale in silico modeling and experimental data predicts CAR-NK cell cytotoxicity across target cell types.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Next-generation CAR-T therapy for acute myeloid leukemia: bridging innovation with clinical translation.Annals of hematology · 2026Review
- Article
- Next-generation CAR-T cells design: leveraging tumor features for enhanced efficacy.Molecular cancer · 2025Review
- Structural Insights into the ADCC Mechanism and Resistance of Mogamulizumab, a First-in-Class Anti-CCR4 Therapy for Cutaneous T Cell Lymphoma.International journal of molecular sciences · 2025Article
- Discovery and preclinical development of a SdAb-based CAR-T technology for targeting CD33 in AML.Molecular therapy. Oncology · 2025Article
- Review
- Recent advances of chimeric antigen receptor T-cell therapy for acute myeloid leukemia.Frontiers in immunology · 2025Review
- Review
- The tandem CD33-CLL1 CAR-T as an approach to treat acute myeloid leukemia.Blood transfusion = Trasfusione del sangueArticle
Corrections and comments
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Authors and funding
19 authors.
Funding
Abstract
backgroundCD33 is a tractable target in acute myeloid leukemia (AML) for chimeric antigen receptor (CAR) T cell therapy, but clinical success is lacking.
methodsWe developed 3P14HLh28Z, a novel CD33-directed CD28/CD3Z-based CAR T cell derived from a high-affinity binder obtained through membrane-proximal fragment immunization in humanized mice.
resultsWe found that immunization exclusively with the membrane-proximal domain of CD33 is necessary for identification of membrane-proximal binders in humanized mice. Compared with clinically validated lintuzumab-based CAR T cells targeting distal CD33 epitopes, 3P14HLh28Z showed enhanced in vitro functionality as well as superior tumor control and increased overall survival in both low antigen density and clinically relevant patient-derived xenograft models. Increased activation and enhanced polyfunctionality led to enhanced efficacy.
conclusionsShowing for the first time that a membrane-proximal CAR is superior to a membrane-distal one in the setting of CD33 targeting, our results demonstrate the rationale for targeting membrane-proximal epitopes with high-affinity binders. We also demonstrate the importance of optimizing CAR T cells for functionality in settings of both low antigen density and clinically relevant patient-derived models.
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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.