ArticleNature communications2024
Split-design approach enhances the therapeutic efficacy of ligand-based CAR-T cells against multiple B-cell malignancies.
Article in Nature communications, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed.
- Recent advances in molecular mechanisms to improve the efficacy of CAR-T cell therapy for viral diseases, cancer, and autoimmune diseases.Stem cell research & therapy · 2026Review
- Design optimization of antibody-ligand motifs to enhance CAR-T redirection activity against solid tumors.Cell reports. Medicine · 2026Article
- Tumor heterogeneity: development, mechanisms, and therapeutic implications.Signal transduction and targeted therapy · 2026Review
- CAR-modified marrow infiltrating lymphocytes efficiently target malignant plasma cells with very low antigen density.Molecular therapy : the journal of the American Society of Gene Therapy · 2026Article
- In Vivo CAR-T Therapies-A New Era of Programmable Immunity.International journal of molecular sciences · 2026Review
- Phosphoproteomic analysis of successive Jurkat CD19-CAR generations reveals TCRζ-driven signalling.Cellular signalling · 2026Article
- Targeting the synovial engine: next-generation engineered immune cells to eradicate pathogenic FLS in rheumatoid arthritis, with safety-first, selective designs.Frontiers in immunology · 2026Review
- BAFF-based trifunctional T-cell engagers trigger robust tumor immunity against B-cell malignancies.Protein & cell · 2025Article
- The Struggle Between Chimeric Antigen Receptor T-Cell Therapy and Neurological Complications in Acute Lymphoblastic Leukemia Treatment.Current issues in molecular biology · 2025Review
- Chimeric antigen receptor T-cell therapy for stiff-person syndrome: bridging innovation and clinical challenges in neuroimmunology.Therapeutic advances in neurological disorders · 2025Review
- SynNotch CAR-T cell, when synthetic biology and immunology meet again.Frontiers in immunology · 2025Review
- CAR-T cell therapy in brain malignancies: obstacles in the face of cellular trafficking and persistence.Frontiers in immunology · 2025Review
Corrections and comments
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Authors and funding
8 authors.
Funding
Abstract
To address immune escape, multi-specific CAR-T-cell strategies use natural ligands that specifically bind multiple receptors on malignant cells. In this context, we propose a split CAR design comprising a universal receptor expressed on T cells and ligand-based switch molecules, which preserves the natural trimeric structure of ligands like APRIL and BAFF. Following optimization of the hinges and switch labeling sites, the split-design CAR-T cells ensure the native conformation of ligands, facilitating the optimal formation of immune synapses between target cancer cells and CAR-T cells. Our CAR-T-cell strategy demonstrates antitumor activities against various B-cell malignancy models in female mice, potentially preventing immune escape following conventional CAR-T-cell therapies in the case of antigen loss or switching. This ligand-based split CAR design introduces an idea for optimizing CAR recognition, enhancing efficacy and potentially improving safety in clinical translation, and may be broadly applicable to cellular therapies based on natural receptors or ligands.
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