ArticleMolecular therapy : the journal of the American Society of Gene Therapy2019
Chimeric Antigen Receptors Incorporating D Domains Targeting CD123 Direct Potent Mono- and Bi-specific Antitumor Activity of T Cells.
Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers, 1 of them a synthesis that pooled it.
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Who cites it
29 citing papers in PubMed, 1 synthesis or guideline pooled it, 42 citations in OpenAlex.
- Mapping the clinical landscape of multifunctional CAR T cells: Targets, trends, and synergies.Molecular therapy : the journal of the American Society of Gene Therapy · 2026Pooled it
- Multi-dimensional orchestration of binders for improved CAR-T immunotherapy.Cancer letters · 2026Review
- Review
- The Current Landscape of Modular CAR T Cells.International journal of molecular sciences · 2025Review
- Fine tuning towards the next generation of engineered T cells.Nature biomedical engineering · 2025Review
- Emerging CAR immunotherapies: broadening therapeutic horizons beyond cancer.Clinical and experimental medicine · 2025Review
- Effectors of the Future: Universal Chimeric Antigen Receptor.Transfusion medicine and hemotherapy : offizielles Organ der Deutschen Gesellschaft fur Transfusionsmedizin und Immunhamatologie · 2025Review
- Targeting BCMA in multiple myeloma: designs, challenges, and future directions.Cancer immunology, immunotherapy : CII · 2025Review
- Review
- Controlling CAR-T cell activity and specificity with synthetic SparX adapters.Molecular therapy : the journal of the American Society of Gene Therapy · 2024Article
- Current Novel Targeted Therapeutic Strategies in Multiple Myeloma.International journal of molecular sciences · 2024Review
- Universal CAR 2.0 to overcome current limitations in CAR therapy.Frontiers in immunology · 2024Review
- Chimeric Antigen Receptor T-Cell Therapy in Acute Myeloid Leukemia: State of the Art and Recent Advances.Cancers · 2023Review
- Immunotherapy of Multiple Myeloma: Current Status as Prologue to the Future.International journal of molecular sciences · 2023Review
- Bringing cell therapy to tumors: considerations for optimal CAR binder design.Antibody therapeutics · 2023Review
- Phase 1 study of CART-ddBCMA for the treatment of subjects with relapsed and refractory multiple myeloma.Blood advances · 2023Article
- [Recent research on chimeric antigen receptor T cells in children with refractory/relapsed acute lymphoblastic leukemia].Zhongguo dang dai er ke za zhi = Chinese journal of contemporary pediatrics · 2023Review
- CD123 a Therapeutic Target for Acute Myeloid Leukemia and Blastic Plasmocytoid Dendritic Neoplasm.International journal of molecular sciences · 2023Review
- Tumor buster - where will the CAR-T cell therapy 'missile' go?Molecular cancer · 2022Review
- Preclinical Efficacy of BCMA-Directed CAR T Cells Incorporating a Novel D Domain Antigen Recognition Domain.Molecular cancer therapeutics · 2022Article
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Chimeric antigen receptor (CAR) T cell therapies have demonstrated impressive initial response rates in hematologic malignancies. However, relapse rates are significant, and robust efficacies in other indications, such as solid tumors, will likely require novel therapeutic strategies and CAR designs. To that end, we sought to develop simple, highly selective targeting domains (D domains) that could be incorporated into complex, multifunctional therapeutics. Herein, we describe the identification and characterization of D domains specific for CD123, a therapeutic target for hematologic malignancies, including acute myelogenous leukemia (AML). CARs comprised of these D domains mediate potent T cell activation and cytolysis of CD123-expressing target cells and induce complete durable remission in two AML xenograft models. We describe a strategy of engineering less immunogenic D domains through the identification and removal of putative T cell epitopes and investigate the binding kinetics and affinity requirements of the resultant D domain CARs. Finally, we extended the utility of D domains by generating functional, bi-specific CARs comprised of a CD123-specific D domain and a CD19-specific scFv. The properties of D domains suggest that this class of targeting domain may facilitate the development of multi-functional CARs where conventional, scFv-based designs may be suboptimal.
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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.