ArticleJournal for immunotherapy of cancer2022
Mesothelin-specific CAR-T cell therapy that incorporates an HLA-gated safety mechanism selectively kills tumor cells.
Article in Journal for immunotherapy of cancer, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT06051695 (A Seamless Phase 1/2 Study to Evaluate the Safety and Efficacy of Mesothelin-Targeting Autologous Logic-gated Tmod™ CAR T Products, in Heterozygous HLA-A*02 Adults With Recurrent Unresectable, Locally Advanced, or Metastatic Solid Tumors That Express MSLN and Have Lost HLA-A*02 Expression), which is not on this map. Cited by 44 papers, 1 of them a synthesis that pooled it.
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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.
A Seamless Phase 1/2 Study to Evaluate the Safety and Efficacy of Mesothelin-Targeting Autologous Logic-gated Tmod™ CAR T Products, in Heterozygous HLA-A*02 Adults With Recurrent Unresectable, Locally Advanced, or Metastatic Solid Tumors That Express MSLN and Have Lost HLA-A*02 Expression
Who cites it
44 citing papers in PubMed, 1 synthesis or guideline pooled it, 62 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
- Cellular immunotherapy for lung cancer: current clinical evidence, translational challenges, and future perspectives: a narrative review.Translational cancer research · 2026Article
- An inducible signal 1 booster overcomes limited access to antigen for solid tumor cell therapy.Molecular therapy. Oncology · 2026Article
- PLP1-triggered NOT gate to address neurotoxicity risk of PSMA-targeted prostate cancer therapy.Journal for immunotherapy of cancer · 2026Article
- Chimeric antigen receptor-macrophages: A new paradigm for cell therapy.Bioengineering & translational medicine · 2026Review
- Systematic functional screening of immunoreceptor tyrosine-based inhibitory motif domains identifies potent inhibitory modules for chimeric antigen receptor-T.Antibody therapeutics · 2026Article
- MyD88-mediated chimaeric antigen receptor macrophages suppress brain metastasis using target-specific phagocytosis.Nature biomedical engineering · 2026Article
- CAR T Cell Therapy in Lung Cancer: Overcoming Tumor Microenvironment-Mediated Barriers.International journal of biological sciences · 2026Review
- CAR-T cell therapy for pancreatic cancer: Translating emerging targets and dual-targeting strategies from solid tumors.Frontiers in immunology · 2026Review
- Novel perspectives on MSLN-targeted cancer therapy: from molecular mechanisms to clinical translation.Cancer biology & therapy · 2025Review
- Endoglin-Directed CAR T Cells Comprehensively Target Tumors in Advanced Sarcomas.Cancer immunology research · 2025Article
- Recent advances and challenges of cellular immunotherapies in lung cancer treatment.Experimental hematology & oncology · 2025Review
- Insights into next-generation immunotherapy designs and tools: molecular mechanisms and therapeutic prospects.Journal of hematology & oncology · 2025Review
- Onboard, tethered IL-12 boosts potency of the Tmod NOT gate and preserves selectivity.Journal for immunotherapy of cancer · 2025Article
- SynNotch CAR-T cell, when synthetic biology and immunology meet again.Frontiers in immunology · 2025Review
- Multi-targeted, NOT gated CAR-T cells as a strategy to protect normal lineages for blood cancer therapy.Frontiers in immunology · 2025Article
- Review
- Review
- Abnormal Cellular Populations Shape Thymic Epithelial Tumor Heterogeneity and Anti-Tumor by Blocking Metabolic Interactions in Organoids.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Beyond CAR-T: The rise of CAR-NK cell therapy in asthma immunotherapy.Journal of translational medicine · 2024Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
13 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundMesothelin (MSLN) is a classic tumor-associated antigen that is expressed in lung cancer and many other solid tumors. However, MSLN is also expressed in normal mesothelium which creates a significant risk of serious inflammation for MSLN-directed therapeutics. We have developed a dual-receptor (Tmod™) system that exploits the difference between tumor and normal tissue in a subset of patients with defined heterozygous gene loss (LOH) in their tumors.
methodsT cells engineered with the MSLN CAR Tmod construct described here contain (1) a novel MSLN-activated CAR and (2) an HLA-A*02-gated inhibitory receptor (blocker). A*02 binding is intended to override T-cell cytotoxicity, even in the presence of MSLN. The Tmod system is designed to treat heterozygous HLA class I patients, selected for HLA LOH. When A*02 is absent from tumors selected for LOH, the MSLN Tmod cells are predicted to mediate potent killing of the MSLN(+)A*02(-) malignant cells.
resultsThe sensitivity of the MSLN Tmod cells is comparable with a benchmark MSLN CAR-T that was active but toxic in the clinic. Unlike MSLN CAR-T cells, the Tmod system robustly protects surrogate "normal" cells even in mixed-cell populations in vitro and in a xenograft model. The MSLN CAR can also be paired with other HLA class I blockers, supporting extension of the approach to patients beyond A*02 heterozygotes.
conclusionsThe Tmod mechanism exemplified by the MSLN CAR Tmod construct provides an alternative route to leverage solid-tumor antigens such as MSLN in safer, more effective ways than previously possible.
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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.