ArticleNature biotechnology2025
Mapping variant effects on anti-tumor hallmarks of primary human T cells with base-editing screens.
Article in Nature biotechnology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 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
30 citing papers in PubMed.
- High-Content CRISPR Screening: Methods and Applications.MedComm · 2026Review
- Deciphering protein mutation-phenotype linkages from CRISPR-based tiling mutagenesis screens.Cell systems · 2026Article
- High-diversity base mutagenesis via simultaneous adenine, cytosine and guanine editing.Nature communications · 2026Article
- Scaled Multidimensional Assays of Variant Effect Identify Sequence-Function Relationships in Hypertrophic Cardiomyopathy.Circulation · 2026Article
- Peptide-MHC-targeted engineered virus-like particles enable selective priming and gene editing of tumor-specific T cells.Cell reports · 2026Article
- Generation of CCR4/CD7 Bispecific CAR-T Cells Resistant to Fratricide and Exhaustion.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- A community machine learning challenge to predict the effects of gene perturbations on T cell differentiation for cancer immunotherapy.bioRxiv : the preprint server for biology · 2026Article
- Inducible, split base editors for in vivo cancer functional genomics.Nature biotechnology · 2026Article
- Single-cell and spatial profiling in cancer biology and clinical oncology.Nature cancer · 2026Review
- Multiplexed assays of variant effect for clinical variant interpretation.Nature reviews. Genetics · 2026Review
- CAR-adapted PIK3CD base editing enhances T cell anti-tumor potency.Nature cancer · 2026Article
- Triple base editor catalyzes saturation mutation of adenine, cytidine, and guanine.Nucleic acids research · 2026Article
- Preparation of human serum albumin-doxorubicin modified carbon nanotubes mediated combined photothermal and chemotherapeutic strategies in melanoma application.Journal of materials science. Materials in medicine · 2025Article
- Next-generation T cell immunotherapies engineered with CRISPR base and prime editing: challenges and opportunities.Nature reviews. Clinical oncology · 2025Review
- Base-editing a single missense mutation in A20 enhances CAR-T cell efficacy.bioRxiv : the preprint server for biology · 2025Article
- Article
- CRISPR tools for T cells: targeting the genome, epigenome, and transcriptome.Trends in cancer · 2025Review
- Challenges and perspectives of CAR-T cell therapy in solid tumours: insights from gastric cancer.British journal of cancer · 2025Review
- Article
- BEscreen: a versatile toolkit to design base editing libraries.Nucleic acids research · 2025Article
Corrections and comments
- Update of
Authors and funding
17 authors.
Funding
Abstract
Single-nucleotide variants (SNVs) in key T cell genes can drive clinical pathologies and could be repurposed to improve cellular cancer immunotherapies. Here, we perform massively parallel base-editing screens to generate thousands of variants at gene loci annotated with known or potential clinical relevance. We discover a broad landscape of putative gain-of-function (GOF) and loss-of-function (LOF) mutations, including in PIK3CD and the gene encoding its regulatory subunit, PIK3R1, LCK, SOS1, AKT1 and RHOA. Base editing of PIK3CD and PIK3R1 variants in T cells with an engineered T cell receptor specific to a melanoma epitope or in different generations of CD19 chimeric antigen receptor (CAR) T cells demonstrates that discovered GOF variants, but not LOF or silent mutation controls, enhanced signaling, cytokine production and lysis of cognate melanoma and leukemia cell models, respectively. Additionally, we show that generations of CD19 CAR T cells engineered with PIK3CD GOF mutations demonstrate enhanced antigen-specific signaling, cytokine production and leukemia cell killing, including when benchmarked against other recent strategies.
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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.