ArticleCancer immunology research2023
Rational Protein Design Yields a CD20 CAR with Superior Antitumor Efficacy Compared with CD19 CAR.
Article in Cancer immunology research, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 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.
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Who cites it
13 citing papers in PubMed, 17 citations in OpenAlex.
- Harnessing macrophage signaling pathways and scalable engineering for next-generation immunotherapies.Signal transduction and targeted therapy · 2026Review
- Fusion Protein Technology to Enhance Pharmacological Properties of L-Asparaginases.Biomolecules · 2026Review
- Cell-autonomous control of CAR signaling and receptor shedding via ADAM17-mediated proteolysis.Cell · 2026Article
- Design of a water-soluble CD20 antigen with computational epitope scaffolding.Protein science : a publication of the Protein Society · 2025Article
- Article
- Tonic signaling in CAR-T therapy: the lever long enough to move the planet.Frontiers of medicine · 2025Review
- IL-13Rα2/TGF-β bispecific CAR-T cells counter TGF-β-mediated immune suppression and potentiate anti-tumor responses in glioblastoma.Neuro-oncology · 2024Article
- CAR spacers: Not just filling space.Molecular therapy : the journal of the American Society of Gene Therapy · 2024Article
- Tonic-ing emissions and compatibility to turbocharge CAR-T.Nature metabolism · 2024Article
- Safety and biological outcomes following a phase 1 trial of GD2-specific CAR-T cells in patients with GD2-positive metastatic melanoma and other solid cancers.Journal for immunotherapy of cancer · 2024Article
- CAR-T cell therapy targeting surface expression of TYRP1 to treat cutaneous and rare melanoma subtypes.Nature communications · 2024Article
- Advancements in cancer immunotherapies targeting CD20: from pioneering monoclonal antibodies to chimeric antigen receptor-modified T cells.Frontiers in immunology · 2024Review
- Refining chimeric antigen receptors via barcoded protein domain combination pooled screening.Molecular therapy : the journal of the American Society of Gene Therapy · 2023Article
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Authors and funding
11 authors at 1 institution in 1 country.
Funding
Abstract
Chimeric antigen receptors (CAR) are fusion proteins whose functional domains are often connected in a plug-and-play manner to generate multiple CAR variants. However, CARs with highly similar sequences can exhibit dramatic differences in function. Thus, approaches to rationally optimize CAR proteins are critical to the development of effective CAR T-cell therapies. Here, we report that as few as two amino-acid changes in nonsignaling domains of a CAR were able to significantly enhance in vivo antitumor efficacy. We demonstrate juxtamembrane alanine insertion and single-chain variable fragment sequence hybridization as two strategies that could be combined to maximize CAR functionality, and describe a CD20 CAR that outperformed the CD19 CAR in antitumor efficacy in preclinical in vitro and in vivo assays. Precise changes in the CAR sequence drove dramatically different transcriptomic profiles upon antigen stimulation, with the most efficacious CAR inducing an enrichment in highly functional memory T cells upon antigen stimulation. These findings underscore the importance of sequence-level optimization to CAR T-cell function, and the protein-engineering strategy described here may be applied to the development of additional CARs against diverse antigens. See related Spotlight by Scheller and Hudecek, p. 142.
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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.