ArticleClinical cancer research : an official journal of the American Association for Cancer Research2019
Multispecific Targeting with Synthetic Ankyrin Repeat Motif Chimeric Antigen Receptors.
Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.
What it found
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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
40 citing papers in PubMed, 55 citations in OpenAlex.
- Multi-dimensional orchestration of binders for improved CAR-T immunotherapy.Cancer letters · 2026Review
- AI-enabled discovery and biochemical optimization of minibinders targeting cancer cell-surface proteins.Nature communications · 2026Article
- Fine tuning towards the next generation of engineered T cells.Nature biomedical engineering · 2025Review
- Engineered SH3-Derived Sherpabodies Function as a Modular Platform for Targeted T-cell Immunotherapy.Cancer research · 2025Article
- Development of multivalent CAR T cells as dual immunotherapy and conditioning agents.Molecular therapy. Oncology · 2025Article
- Future perspectives on novel CAR-T therapeutics beyond CD19 and BCMA in onco-hematology.Frontiers in immunology · 2025Review
- Engineering the next generation of CAR T- cells: precision modifications, logic gates and universal strategies to overcome exhaustion and tumor resistance.Frontiers in oncology · 2025Review
- A new evidence-based design-of-experiments approach for optimizing drug delivery systems with exemplification by emulsion-derived Vancomycin-loaded PLGA capsules.Scientific reports · 2024Article
- The physical landscape of CAR-T synapse.Biophysical journal · 2024Review
- Beyond CAR-T: The rise of CAR-NK cell therapy in asthma immunotherapy.Journal of translational medicine · 2024Review
- Synthetic biology approaches for improving the specificity and efficacy of cancer immunotherapy.Cellular & molecular immunology · 2024Review
- Synthetic Gene Circuits for Regulation of Next-Generation Cell-Based Therapeutics.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Review
- Advances in CAR T cell therapy: antigen selection, modifications, and current trials for solid tumors.Frontiers in immunology · 2024Review
- AAV vectors displaying bispecific DARPins enable dual-control targeted gene delivery.Biomaterials · 2023Article
- Chimeric antigen receptor-natural killer cells: a promising sword against insidious tumor cells.Human cell · 2023Review
- Compromised antigen binding and signaling interfere with bispecific CD19 and CD79a chimeric antigen receptor function.Blood advances · 2023Article
- Programming CAR T Cell Tumor Recognition: Tuned Antigen Sensing and Logic Gating.Cancer discovery · 2023Article
- Advancements in CAR-NK therapy: lessons to be learned from CAR-T therapy.Frontiers in immunology · 2023Review
- Current progress in CAR-T cell therapy for tumor treatment.Oncology letters · 2022Review
- Protein scaffolds: antibody alternatives for cancer diagnosis and therapy.RSC chemical biology · 2022Review
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 2 countries.
Funding
Abstract
purposeThe outgrowth of antigen-negative variants is a significant challenge for adoptive therapy with T cells that target a single specificity. Chimeric antigen receptors (CAR) are typically designed with one or two scFvs that impart antigen specificity fused to activation and costimulation domains of T-cell signaling molecules. We designed and evaluated the function of CARs with up to three specificities for overcoming tumor escape using Designed Ankyrin Repeat Proteins (DARPins) rather than scFvs for tumor recognition. EXPERIMENTAL
designA monospecific CAR was designed with a DARPin binder (E01) specific for EGFR and compared with a CAR designed using an anti-EGFR scFv. CAR constructs in which DARPins specific for EGFR, EpCAM, and HER2 were linked together in a single CAR were then designed and optimized to achieve multispecific tumor recognition. The efficacy of CAR-T cells bearing a multispecific DARPin CAR for treating tumors with heterogeneous antigen expression was evaluated
resultsThe monospecific anti-EGFR E01 DARPin conferred potent tumor regression against EGFR
conclusionsDARPins can serve as high-affinity recognition motifs for CAR design, and their robust architecture enables linking of multiple binders against different antigens to achieve functional synergy and reduce antigen escape.
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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.