ArticleMolecular therapy : the journal of the American Society of Gene Therapy2020
A Functional Screening Strategy for Engineering Chimeric Antigen Receptors with Reduced On-Target, Off-Tumor Activation.
Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2020. 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
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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, 32 citations in OpenAlex.
- Drug-controlled CAR T cells through the regulation of cell-cell interactions.Nature chemical biology · 2026Article
- Fast analysis and engineering of protein function by microbe-independent deep assembly and screening.Molecular systems biology · 2026Article
- The evolution of display technologies for antibody drug discovery.Trends in biotechnology · 2026Review
- Enhancing CAR-T cell activity prediction via fine-tuning protein language models with generated CAR sequences.BMC bioinformatics · 2026Article
- Single-Target Pairing System (StarPair) for Large-Scale Interrogation of Cell-Cell Interactions.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- High-throughput screening to engineer optimal T cell therapies: current knowledge and future prospects.Frontiers in oncology · 2026Review
- Advancing Cancer Immunotherapy: Chimeric Antigen Receptor (CAR)-T Cell Engineering through Novel Screening Methods.Biomolecules & therapeutics · 2026Review
- Preclinical development and selection of nanobody-based CAR-T cells targeting HER2-positive solid tumors.Molecular therapy. Oncology · 2025Article
- Article
- Expanding the CAR toolbox with high throughput screening strategies for CAR domain exploration: a comprehensive review.Journal for immunotherapy of cancer · 2025Review
- Mathematical models and computational approaches in CAR-T therapeutics.Frontiers in immunology · 2025Review
- Challenges and future perspectives for high-throughput chimeric antigen receptor T cell discovery.Current opinion in biotechnology · 2024Review
- High-throughput screening for optimizing adoptive T cell therapies.Experimental hematology & oncology · 2024Review
- Regulation of CAR transgene expression to design semiautonomous CAR-T.Molecular therapy. Oncology · 2024Review
- Influencing factors and solution strategies of chimeric antigen receptor T-cell therapy (CAR-T) cell immunotherapy.Oncology research · 2024Review
- Deep mutational scanning of proteins in mammalian cells.Cell reports methods · 2023Review
- Refining chimeric antigen receptors via barcoded protein domain combination pooled screening.Molecular therapy : the journal of the American Society of Gene Therapy · 2023Article
- Bringing cell therapy to tumors: considerations for optimal CAR binder design.Antibody therapeutics · 2023Review
- Synthesizing a Smarter CAR T Cell: Advanced Engineering of T-cell Immunotherapies.Cancer immunology research · 2023Article
- speedingCARs: accelerating the engineering of CAR T cells by signaling domain shuffling and single-cell sequencing.Nature communications · 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
8 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
In recent years, chimeric antigen receptor (CAR) T cell cancer immunotherapies have advanced substantially in the clinic. However, challenges related to safety persist; one major concern occurs when CARs trigger a response to antigen present on healthy cells (on-target, off-tumor response). A strategy to ameliorate this relies on the complex relationship between receptor affinity and signaling, such that one can engineer a CAR that is only activated by tumor cells expressing high antigen levels. Here, we developed a CAR T cell display platform with stable genomic expression and rapid functional screening based on interleukin-2 signaling. Starting with a CAR with high affinity toward its target antigen, we combined CRISPR-Cas9 genome editing and deep mutational scanning to generate a library of antigen-binding domain variants. This library was subjected to multiple rounds of selection based on either antigen binding or cell signaling. Deep sequencing of the resulting libraries and a comparative analysis revealed the enrichment and depletion of specific variants from which we selected CARs that were selectively activated by tumor cells based on antigen expression levels. Our platform demonstrates how directed evolution based on functional screening and deep sequencing-guided selection can be combined to enhance the selectivity and safety of CARs.
Indexed as
Identifiers
What OpenQuestion holds
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.