ArticleCellular & molecular immunology2021
Phase I study of CAR-T cells with PD-1 and TCR disruption in mesothelin-positive solid tumors.
Article in Cellular & molecular immunology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 174 papers, 2 of them syntheses that pooled it.
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
174 citing papers in PubMed, 2 syntheses or guidelines pooled it, 245 citations in OpenAlex.
- Mapping the clinical landscape of multifunctional CAR T cells: Targets, trends, and synergies.Molecular therapy : the journal of the American Society of Gene Therapy · 2026Pooled it
- The synergistic immunotherapeutic impact of engineered CAR-T cells with PD-1 blockade in lymphomas and solid tumors: a systematic review.Frontiers in immunology · 2024Pooled it
- Immune checkpoint knockout screen reveals TIGIT-CD155 interaction as a significant modulator of adapter CAR-T cell function in acute myeloid leukemia.Oncoimmunology · 2026Article
- CRISPR in clinical oncology: translational advances from molecular diagnostics to therapeutics.Nature reviews. Clinical oncology · 2026Review
- Augmenting CAR T cell functionality and metabolism through CD39 downtuning.Molecular therapy. Oncology · 2026Article
- Barriers and Blueprints: Next-Generation Engineering Strategies for CAR-T Cell Therapy in Gastrointestinal Tumors.Pharmaceuticals (Basel, Switzerland) · 2026Review
- The landscape and trajectory of global CRISPR therapeutics.Molecular therapy. Nucleic acids · 2026Review
- Chimeric antigen receptor (CAR)-T cell therapy for solid tumors in pediatric patients: current breakthroughs, dilemmas, and strategies.Experimental hematology & oncology · 2026Review
- Recent Advances in CRISPR/Cas Technologies for Biological Discovery, Therapeutics, and Diagnostics.Biomolecules · 2026Review
- A 38-color spectral panel for cost efficient characterization of T cell therapy products.Cytotherapy · 2026Article
- The TCR in CAR T cell therapy: use it or lose it?Cancer gene therapy · 2026Review
- Genetic Interruption of PD-1/PD-L1 as an Alternative Means for Immune Checkpoint Blockade in Cancer: A Review.Pharmaceutics · 2026Review
- Prime Editing, CRISPR-Cas9, and NanoCas Genome Editing for Cancer Treatment.Molecular biotechnology · 2026Review
- The genome takes the wheel: CAR T with built-in circuits.Immuno-oncology technology · 2026Article
- Emerging strategies to reduce the side effects of CAR-T cell therapy: focusing on gene editing and nanotechnology.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2026Review
- Transforming tumor microenvironments: nanotechnology and gene therapy in cellular signaling and epigenetic insight into chemo-resistance.Journal of experimental & clinical cancer research : CR · 2026Review
- DNA and RNA editing for the therapy of human diseases: current status, challenges, and future prospects.Molecular biomedicine · 2026Review
- Safe and Efficient CRISPR Genome Editing of Primary Human T Cells Using a Droplet-Based Cell Mechanoporation Platform.Small (Weinheim an der Bergstrasse, Germany) · 2026Article
- Article
- Mesothelin biology and the evolving landscape of targeted immunotherapy.Molecular therapy. Oncology · 2026Review
114 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
17 authors at 4 institutions in 2 countries.
Funding
Abstract
Programmed cell death protein-1 (PD-1)-mediated immunosuppression has been proposed to contribute to the limited clinical efficacy of chimeric antigen receptor T (CAR-T) cells in solid tumors. We generated PD-1 and T cell receptor (TCR) deficient mesothelin-specific CAR-T (MPTK-CAR-T) cells using CRISPR-Cas9 technology and evaluated them in a dose-escalation study. A total of 15 patients received one or more infusions of MPTK-CAR-T cells without prior lymphodepletion. No dose-limiting toxicity or unexpected adverse events were observed in any of the 15 patients. The best overall response was stable disease (2/15 patients). Circulating MPTK-CAR-T cells peaked at days 7-14 and became undetectable beyond 1 month. TCR-positive CAR-T cells rather than TCR-negative CAR-T cells were predominantly detected in effusion or peripheral blood from three patients after infusion. We further confirmed the reduced persistence of TCR-deficient CAR-T cells in animal models. Our results establish the preliminary feasibility and safety of CRISPR-engineered CAR-T cells with PD-1 disruption and suggest that the natural TCR plays an important role in the persistence of CAR-T cells when treating solid tumors.
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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.