ReviewThe FEBS journal2021
Driving CARs with alternative navigation tools - the potential of engineered binding scaffolds.
Review in The FEBS journal, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
24 citing papers in PubMed.
- Design optimization of antibody-ligand motifs to enhance CAR-T redirection activity against solid tumors.Cell reports. Medicine · 2026Article
- Cell Surface Markers of Mesenchymal Stem Cells: Current Knowledge and Advances in Characterization Technologies.Life (Basel, Switzerland) · 2025Review
- Global research trends in CAR-T cell therapy for glioblastoma: a bibliometric and visualized analysis.Discover oncology · 2025Article
- Ligand-Based CAR-T Cells Targeting EGFR Exhibit Favorable Antitumor Effects Against Gynecologic Malignancies.Cancer science · 2025Article
- Engineered SH3-Derived Sherpabodies Function as a Modular Platform for Targeted T-cell Immunotherapy.Cancer research · 2025Article
- Targeting BCMA in multiple myeloma: designs, challenges, and future directions.Cancer immunology, immunotherapy : CII · 2025Review
- Nanobody-based CAR NK cells for possible immunotherapy of MICAPNAS nexus · 2024Article
- An engineering strategy to target activated EGFR with CAR T cells.Cell reports methods · 2024Article
- Exosome-mimetic vesicles derived from fibroblasts carrying matrine for wound healing.Burns & trauma · 2024Article
- MICA-specific nanobodies for diagnosis and immunotherapy of MICAFrontiers in immunology · 2024Article
- Solving the mystery of the FMC63-CD19 affinity.Scientific reports · 2023Article
- Empowering gene delivery with protein engineering platforms.Gene therapy · 2023Review
- Evolution and synthetic biology.Current opinion in microbiology · 2023Review
- Exploiting the Features of Short Peptides to Recognize Specific Cell Surface Markers.International journal of molecular sciences · 2023Article
- Bringing cell therapy to tumors: considerations for optimal CAR binder design.Antibody therapeutics · 2023Review
- Tuning CARs: recent advances in modulating chimeric antigen receptor (CAR) T cell activity for improved safety, efficacy, and flexibility.Journal of translational medicine · 2023Review
- Ligand-based targeting of c-kit using engineered γδ T cells as a strategy for treating acute myeloid leukemia.Frontiers in immunology · 2023Article
- Current updates on generations, approvals, and clinical trials of CAR T-cell therapy.Human vaccines & immunotherapeutics · 2022Article
- Rapid Covalent Labeling of Membrane Proteins on Living Cells Using a Nanobody-Epitope Tag Pair.Bioconjugate chemistry · 2022Article
- Dopamine DBiomolecules · 2022Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors.
Funding
Abstract
T cells that are genetically engineered to express chimeric antigen receptors (CAR T cells) have shown impressive clinical efficacy against B-cell malignancies. In contrast to these highly potent CD19-targeting CAR T cells, many of those directed against other tumor entities and antigens currently suffer from several limitations. For example, it has been demonstrated that many scFvs used as antigen-binding domains in CARs show some degree of oligomerization, which leads to tonic signaling, T cell exhaustion, and poor performance in vivo. Therefore, in many cases alternatives to scFvs would be beneficial. Fortunately, due to the development of powerful protein engineering technologies, also non-immunoglobulin-based scaffolds can be engineered to specifically recognize antigens, thus eliminating the historical dependence on antibody-based binding domains. Here, we discuss the advantages and disadvantages of such engineered binding scaffolds, in particular with respect to their application in CARs. We review recent studies, collectively showing that there is no functional or biochemical aspect that necessitates the use of scFvs in CARs. Instead, antigen recognition can also be mediated efficiently by engineered binding scaffolds, as well as natural ligands or receptors fused to the CAR backbone. Finally, we critically discuss the risk of immunogenicity and show that the extent of nonhuman amino acid stretches in engineered scaffolds-even in those based on nonhuman proteins-is more similar to humanized scFvs than might be anticipated. Together, we expect that engineered binding scaffolds and natural ligands and receptors will be increasingly used for the design of CAR T cells.
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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.