ArticleMolecular therapy : the journal of the American Society of Gene Therapy2025
Computational structural optimization enhances IL13Rα2 - B7-H3 tandem CAR T cells to overcome antigen-heterogeneity-mediated tumor escape.
Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers, 1 of them a synthesis that pooled it.
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Who cites it
12 citing papers in PubMed, 1 synthesis or guideline pooled it.
- 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
- Engineering the next generation of cellular therapies for solid tumors: multi-specific armored CARs and TME reprogramming strategies.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2026Review
- CAR T cell therapy beyond cancer: current status, challenges and future prospects.Signal transduction and targeted therapy · 2026Review
- B7 homolog 3-targeted CAR-T cells secreting EGFR T-cell engagers for improved control of glioblastoma progression.Molecular biomedicine · 2026Article
- A Comprehensive Evaluation of CAR-T Cell Gene Therapy, Tracing its Revolutionary Clinical Breakthroughs and Advancements Towards Next-Generation Engineering.Expert reviews in molecular medicine · 2026Review
- Beyond CRISPR: next-gen precision engineering of CAR-NK cells for enhanced persistence, trafficking, and tumor eradication.Cancer cell international · 2026Review
- Plying potency assays for immunotherapy of solid tumors.Frontiers in immunology · 2026Review
- Advancing breast cancer treatment through dual targeting CAR T cell therapy.Discover oncology · 2025Review
- CAR T-cell therapy for meningioma: Mesothelin emerges as a novel promising target.Neuro-oncology · 2025Article
- Computational optimization of chimeric antigen receptor.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Article
- CAR-iNKT cells for cancer therapy: a comprehensive review of engineering, mechanisms, and clinical progress.ImmunotherapyReview
Corrections and comments
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Authors and funding
10 authors.
Funding
Abstract
Chimeric antigen receptor (CAR) T cell therapy is a highly effective treatment for multiple malignancies. However, one limitation is tumor antigen-heterogeneity and downregulation, which allows tumor cells to evade conventional, monospecific CAR T cells. One approach to overcome this tumor escape is by utilizing a tandem CAR recognizing two antigens. However, tandem CAR constructs often require optimization to achieve cell surface expression and function. Herein, we describe our process of designing an IL-13Rα2-B7-H3 tandem CAR. Interestingly, our original tandem CAR failed to express on the cell surface, leading to a systematic evaluation of 24 tandem constructs varying in their scFv positioning, linkers, and specific amino acids. We identified a "trouble region" in the CAR and optimized it using computational approaches, rescuing surface expression and improving function compared with monospecific CAR T cells. Further, the optimized tandem CAR T cells more effectively eliminated tumors than monospecific CAR T cells in vivo. Our study demonstrates the successful application of structure-guided computational strategies to restore surface expression and antitumor efficacy of an IL13Rα2 - B7-H3 tandem CAR. Our study also highlights the necessity of computational methods to guide the design of synthetic proteins, and that these methods can increase CAR T cell efficacy.
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Registered trials
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