ArticleGenome medicine2024
Efficacy and safety of novel multiple-chain DAP-CAR-T cells targeting mesothelin in ovarian cancer and mesothelioma: a single-arm, open-label and first-in-human study.
Article in Genome medicine, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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The trial behind it
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Who cites it
13 citing papers in PubMed.
- Immuno-PET imaging of mesothelin in ovarian cancer withBiomarker research · 2026Article
- Overcoming Therapy Resistance in Ovarian Cancer: From Molecular Mechanisms to Emerging Therapeutic Strategies.Cancers · 2026Review
- Mapping clinical CAR-T cells: insights from scRNA-seq.Trends in molecular medicine · 2026Review
- Hidden in plain sight: a narrative review on environmental exposures and the fight against mesothelioma.Journal of thoracic disease · 2026Review
- Advances in adoptive cell therapy for ovarian cancer.Frontiers in immunology · 2026Review
- Harnessing the immune system: future directions in cancer immunotherapy.Frontiers in immunology · 2026Review
- Novel perspectives on MSLN-targeted cancer therapy: from molecular mechanisms to clinical translation.Cancer biology & therapy · 2025Review
- Nanomedicine in Ovarian Cancer: Advances in Imaging, Targeted Delivery, and Theranostic Therapeutic Platforms.Cancers · 2025Review
- Comprehensive single-cell transcriptome landscape of metastatic colorectal cancer identifies budding-potential cells and their interactions with cancer-associated fibroblasts.NPJ precision oncology · 2025Article
- Challenges and perspectives of CAR-T cell therapy in solid tumours: insights from gastric cancer.British journal of cancer · 2025Review
- Review
- Therapeutic landscape of ovarian cancer: recent advances and emerging therapies.Biomarker research · 2025Review
- The dual nature of immunotherapy in female reproductive disorders: immune homeostasis and clinical challenges.Frontiers in immunology · 2025Review
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Authors and funding
16 authors.
Funding
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Abstract
backgroundDespite remarkable achievements in applying chimeric antigen receptor (CAR)-T cells to treat hematological malignancies, they remain much less effective against solid tumors, facing several challenges affecting their clinical use. We previously showed that multichain DNAX-activating protein (DAP) CAR structures could enhance the safety and efficacy of CAR-T cells when used against solid tumors. In particular, mesothelin (MSLN)-targeted CAR-T cell therapy has therapeutic potential in MSLN-positive solid tumors, including ovarian cancer and mesothelioma.
methodsIn vitro cell killing assays and xenograft model were utilized to determine the anti-tumor efficacy of MSLN targeting DAP-CAR-T cells and other CAR-T cells. ELISA and flow cytometry analysis were used to assess the cytokine secretion capacity and proliferation ability. Eight patients with MSLN expression were enrolled to evaluate the safety and efficacy of MSLN-DAP CAR-T cell therapy. Single-cell sequencing was performed to explore the dynamics of immune cells in patients during treatment and to identify the transcriptomic signatures associated with efficacy and toxicity.
resultsWe found that multichain DAP-CAR formed by combining a natural killer cell immunoglobulin-like receptor truncator and DAP12 exhibited better cytotoxicity and tumor-killing capacity than other natural killer cell-activated receptors associated with DAP12, DAP10, or CD3Z. The safety and efficacy of MSLN-DAP CAR-T cell therapy in patients with ovarian cancer and mesothelioma were evaluated in a single-arm, open-label clinical trial (ChiCTR2100046544); two patients achieved partial response, while four patients had a stable disease status. Furthermore, single-cell sequencing analysis indicated that KT032 CAR-T cell infusion could recruit more immune cells and temporarily remodel the TME.
conclusionsOur study highlights the safety and therapeutic efficacy of multiple-chain DAP-CAR-T cell therapy targeting MSLN to treat patients with ovarian cancer and mesothelioma.
trial registrationChiCTR.org.cn, ChiCTR2100046544 . May 21, 2021.
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