ArticleMolecular cancer therapeutics2022
Development of Highly Effective Anti-Mesothelin hYP218 Chimeric Antigen Receptor T Cells With Increased Tumor Infiltration and Persistence for Treating Solid Tumors.
Article in Molecular cancer therapeutics, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
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Who cites it
36 citing papers in PubMed, 46 citations in OpenAlex.
- Review
- Barriers and Blueprints: Next-Generation Engineering Strategies for CAR-T Cell Therapy in Gastrointestinal Tumors.Pharmaceuticals (Basel, Switzerland) · 2026Review
- Palliative Systemic Therapy in Advanced Thymic Epithelial Tumors in 2026-A Narrative Review.Cancers · 2026Review
- Rapid CAR screening and circRNA-driven CAR-NK cells for persistent shed-resistant immunotherapy.Signal transduction and targeted therapy · 2026Article
- Preclinical development of mesothelin-targeting CAR T cells for the treatment of cholangiocarcinoma.Hepatology communications · 2026Article
- Advancing Cancer Immunotherapy: Chimeric Antigen Receptor (CAR)-T Cell Engineering through Novel Screening Methods.Biomolecules & therapeutics · 2026Review
- Review
- Mesothelin-directed protein-drug conjugates for mesothelin-low solid tumor therapy.Nature communications · 2025Article
- Non-pathogenic E. coli displaying decoy-resistant IL18 mutein boosts anti-tumor and CAR NK cell responses.Nature biotechnology · 2025Article
- Review
- Biomimetic Tumour Model Systems for Pancreatic Ductal Adenocarcinoma in Relation to Photodynamic Therapy.International journal of molecular sciences · 2025Review
- Robust differentiation of NK cells from MSLN.CAR-IL-15-engineered human iPSCs with enhanced antitumor efficacy against solid tumors.Science advances · 2025Article
- Development of CAR-T Therapies and Personalized Vaccines for the Treatment of Cholangiocarcinoma: Current Progress, Mechanisms of Action, and Challenges.The American journal of pathology · 2025Review
- Muc16CD is a novel CAR T cell target antigen for the treatment of pancreatic cancer.Molecular therapy. Oncology · 2024Article
- Persistence of activated anti-mesothelin hYP218 chimeric antigen receptor T cells in the tumour is associated with efficacy in gastric and colorectal carcinomas.Clinical and translational medicine · 2024Article
- rhIL-7-hyFc, a long-acting interleukin-7, improves efficacy of CAR-T cell therapy in solid tumors.Journal for immunotherapy of cancer · 2024Article
- Application of CAR-T cell therapy targeting mesothelin in solid tumor treatment.Discover oncology · 2024Review
- CAR memory-like NK cells targeting the membrane proximal domain of mesothelin demonstrate promising activity in ovarian cancer.Science advances · 2024Article
- A Bispecific Antibody That Targets the Membrane-Proximal Region of Mesothelin and Retains High Anticancer Activity in the Presence of Shed Mesothelin.Molecular cancer therapeutics · 2024Article
- Current and future immunotherapeutic approaches in pancreatic cancer treatment.Journal of hematology & oncology · 2024Review
Corrections and comments
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Authors and funding
12 authors at 1 institution in 1 country.
Funding
Abstract
Mesothelin targeting CAR T cells have limited activity in patients. In this study, we sought to determine if efficacy of anti-mesothelin CAR T cells is dependent on the mesothelin epitopes that are recognized by them. To do so, we developed hYP218 (against membrane-proximal epitope) and SS1 (against membrane-distal epitope) CAR T cells. Their efficacy was assessed in vitro using mesothelin-positive tumor cell lines and in vivo in NSG mice with mesothelin-expressing ovarian cancer (OVCAR-8), pancreatic cancer (KLM-1), and mesothelioma patient-derived (NCI-Meso63) tumor xenografts. Persistence and tumor infiltration of CAR T cells was determined using flow cytometry. hYP218 CAR T cells killed cancer cells more efficiently than SS1 CAR T cells, with a two- to fourfold lower ET50 value (effector-to-target ratio for 50% killing of tumor cells). In mice with established tumors, single intravenous administration of hYP218 CAR T cells lead to improved tumor response and survival compared with SS1 CAR T cells, with complete regression of OVCAR-8 and NCI-Meso63 tumors. Compared with SS1 CAR T cells, there was increased peripheral blood expansion, persistence, and tumor infiltration of hYP218 CAR T cells in the KLM-1 tumor model. Persistence of hYP218 CAR T cells in treated mice led to antitumor immunity when rechallenged with KLM-1 tumor cells. Our results show that hYP218 CAR T cells, targeting mesothelin epitope close to cell membrane, are very effective against mesothelin-positive tumors and are associated with increased persistence and tumor infiltration. These results support its clinical development to treat patients with mesothelin-expressing cancers.
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