ArticleCancer immunology, immunotherapy : CII2023
Dual CAR-T cells to treat cancers co-expressing NKG2D and PD1 ligands in xenograft models of peritoneal metastasis.
Article in Cancer immunology, immunotherapy : CII, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 24 citations in OpenAlex.
- Anti-PD-1 single-chain variable fragments in cancer immunotherapy: from molecular engineering to clinical translation.Cancer chemotherapy and pharmacology · 2026Review
- Innovative immunotherapy approaches: harnessing synergy of dual checkpoint blockade in oncology.Naunyn-Schmiedeberg's archives of pharmacology · 2026Review
- Targeting NKG2D/NKG2DL axis in cancer immunotherapy: mechanisms and therapeutic applications.Journal of translational medicine · 2026Review
- Optimizing CAR T cell therapy for solid tumours: a clinical perspective.Nature reviews. Clinical oncology · 2025Review
- Exploring transposable elements: new horizons in cancer diagnostics and therapeutics.Mobile DNA · 2025Review
- Enhancing CAR T-Cell Function with Domains of Innate Immunity Sensors.International journal of molecular sciences · 2025Review
- Advancements in cellular immunotherapy: overcoming resistance in lung and colorectal cancer.Frontiers in immunology · 2025Review
- Designs of NKG2D-based immunotherapeutics for cancer.Frontiers in immunology · 2025Review
- From molecular design to clinical translation: dual-targeted CAR-T strategies in cancer immunotherapy.International journal of biological sciences · 2025Review
- CAR-T cell therapy: Advances in digestive system malignant tumors.Molecular therapy. Oncology · 2024Review
- T cells with split CARs specific for NKG2D ligands and PD-L1 exhibit improved selectivity towards monocyte-derived cells while effective in eliminating acute myeloid leukaemia in vivo.Journal of cancer research and clinical oncology · 2023Article
- Comparative Pre-Clinical Analysis of CD20-Specific CAR T Cells Encompassing 1F5-, Leu16-, and 2F2-Based Antigen-Recognition Moieties.International journal of molecular sciences · 2023Article
- CAR-T cell immunotherapy for ovarian cancer: hushing the silent killer.Frontiers in immunology · 2023Review
- Efficacy evaluation of multi-immunotherapy in ovarian cancer: From bench to bed.Frontiers in immunology · 2022Review
- Recent advances in CAR-T cells therapy for colorectal cancer.Frontiers in immunology · 2022Review
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 2 countries.
Funding
Abstract
While the expression of either NKG2D ligands or PD-1 ligands has been reported in various types of cancers, the co-expression of the two sets of ligands in the same tumour tissues is still un-investigated. After examining 68 primary ovarian cancer samples, we observed around 80% of the co-expression in low grade serous and endometrioid ovarian cancer samples. We then constructed a dual CAR system that splits the conventional single-input of a 2nd generation CAR into two independent chimeric receptors, one composed of the NKG2D extracellular domain linked with DAP12 for T cell activation and another using the PD-1 extracellular domain linked with 4-1BB for costimulatory signal 2 input. Given the limitation of the low-affinity PD-1 receptor in recognizing cancer cells with low levels of PD-1 ligands, we also used a high-affinity scFv specific to PD-L1 in our combinatorial approach to expand the range of target cancer cells with different expression levels of PD-L1. The two types of dual CAR-T cells were generated through electroporation of non-viral piggyBac transposon plasmids and were effective in eliminating the target cancer cells. Especially, the dual CAR-T cells with anti-PD-L1 scFv were capable of eradicating established tumors in mouse models of peritoneal metastasis of colorectal cancer and ovarian cancer. Since both NKG2D ligands and PD-1 ligands have been marked as favourable cancer therapeutic targets, the new dual CAR-T cells developed in this study hold attractive application potential in treating metastatic peritoneal carcinoma.
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