ArticleScience translational medicine2014
Regional delivery of mesothelin-targeted CAR T cell therapy generates potent and long-lasting CD4-dependent tumor immunity.
Article in Science translational medicine, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 375 papers, 1 of them a synthesis 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
375 citing papers in PubMed, 1 synthesis or guideline pooled it, 559 citations in OpenAlex.
- The safety and efficacy of chimeric antigen receptor-T cell therapy in solid malignancies: a systematic review and meta-analysis.Frontiers in immunology · 2026Pooled it
- Ad-SGE-DKK3 Gene Therapy Overcomes Resistance to Immune Checkpoint Blockade in Pleural Mesothelioma.Clinical cancer research : an official journal of the American Association for Cancer Research · 2025Trial
- Safety and Tolerability of Letetresgene Autoleucel (GSK3377794): Pilot Studies in Patients with Advanced Non-Small Cell Lung Cancer.Clinical cancer research : an official journal of the American Association for Cancer Research · 2025Trial
- Pharmacodynamic changes in tumor and immune cells drive iberdomide's clinical mechanisms of activity in relapsed and refractory multiple myeloma.Cell reports. Medicine · 2024Trial
- Why CD4+ T cells matter in adoptive cell therapy for solid cancers.Immuno-oncology technology · 2026Review
- Cord Blood-Derived Fibroblast Activation Protein-Targeted Chimeric Antigen Receptor Natural Killer Cells Persist in Vivo.Cancer science · 2026Article
- Supramolecular immunomodulatory hydrogelator potentiates CAR-T therapy with long-lasting endogenous immunity toward solid tumor eradication.Science advances · 2026Article
- Depletion of CD8Molecular therapy : the journal of the American Society of Gene Therapy · 2026Article
- CAR-T and TIL therapies in solid tumors: barriers, clinical lessons, and convergent solutions.Cancer cell international · 2026Review
- IL7-Receptor-Targeted CAR T-Cell Therapy for T-Cell Acute Lymphoblastic Leukemia.Nature communications · 2026Article
- Loss of tumor suppressor NF2 mediates resistance to CAR T cell and anti-PD-1 therapy: Strategies to restore immunotherapy sensitivity.Med (New York, N.Y.) · 2026Article
- Irreversible Electroporation Enhances Solid Tumor Infiltration and Selective Cancer Cell Lysis by CAR T Cells.Clinical cancer research : an official journal of the American Association for Cancer Research · 2026Article
- Advances in the management of metastatic gastric cancer: current strategies and emerging therapeutics.Nature reviews. Clinical oncology · 2026Review
- Membrane-bound TRAIL-armoring augments CAR-T cells in mesothelin-positive solid malignancies.Journal for immunotherapy of cancer · 2026Article
- A Comprehensive Evaluation of CAR-T Cell Gene Therapy, Tracing its Revolutionary Clinical Breakthroughs and Advancements Towards Next-Generation Engineering.Expert reviews in molecular medicine · 2026Review
- Computational identification of migrating T cells in spatial transcriptomics data.JCI insight · 2026Article
- Rethinking Advanced Renal Cell Carcinoma: Integrative Genomics, Immunotherapy, and Molecular-Orthomolecular Strategies.Cancers · 2026Review
- Application of CAR-T therapy in solid tumors: current opportunities and challenges.Cancer gene therapy · 2026Review
- Beyond CAR-T and oncology: broadening chimeric antigen receptor technologies across cell types and diseases.Precision clinical medicine · 2026Review
- Pleural Mesothelioma: Current Therapeutic Strategies and Future Directions.Current oncology reports · 2026Review
315 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
8 authors at 2 institutions in 1 country.
Funding
Abstract
Translating the recent success of chimeric antigen receptor (CAR) T cell therapy for hematological malignancies to solid tumors will necessitate overcoming several obstacles, including inefficient T cell tumor infiltration and insufficient functional persistence. Taking advantage of an orthotopic model that faithfully mimics human pleural malignancy, we evaluated two routes of administration of mesothelin-targeted T cells using the M28z CAR. We found that intrapleurally administered CAR T cells vastly outperformed systemically infused T cells, requiring 30-fold fewer M28z T cells to induce long-term complete remissions. After intrapleural T cell administration, prompt in vivo antigen-induced T cell activation allowed robust CAR T cell expansion and effector differentiation, resulting in enhanced antitumor efficacy and functional T cell persistence for 200 days. Regional T cell administration also promoted efficient elimination of extrathoracic tumor sites. This therapeutic efficacy was dependent on early CD4(+) T cell activation associated with a higher intratumoral CD4/CD8 cell ratios and CD28-dependent CD4(+) T cell-mediated cytotoxicity. In contrast, intravenously delivered CAR T cells, even when accumulated at equivalent numbers in the pleural tumor, did not achieve comparable activation, tumor eradication, or persistence. The ability of intrapleurally administered T cells to circulate and persist supports the concept of delivering optimal CAR T cell therapy through "regional distribution centers." On the basis of these results, we are opening a phase 1 clinical trial to evaluate the safety of intrapleural administration of mesothelin-targeted CAR T cells in patients with primary or secondary pleural malignancies.
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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.