The second generation of mesothelin targeted CAR-T cells that secret a fusion protein of IL21 and scfv against PD1 have been constructed and their anti-cancer function has been verified by multiple in vitro and in vivo studies. Clinical studies will be performed to test anti-cancer function of the CAR-T cells for immunotherapy of human cancer patients with Mesothelin expressions. In this phase I study, the safety, tolerance, and preliminary efficacy of the Mesothelin-CAR-T cell immunotherapy on human cancers will firstly be evaluated.

开始日期2023-03-10

申办/合作机构

广州医科大学附属第二医院

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100 项与 Mesothelin targeted CAR-T cells(Fapon Biotherapy) 相关的临床结果

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100 项与 Mesothelin targeted CAR-T cells(Fapon Biotherapy) 相关的转化医学

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100 项与 Mesothelin targeted CAR-T cells(Fapon Biotherapy) 相关的专利（医药）

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项与 Mesothelin targeted CAR-T cells(Fapon Biotherapy) 相关的文献（医药）

2023-10-04·Cancer immunology research

Tumor-Targeted Nonablative Radiation Promotes Solid Tumor CAR T-cell Therapy Efficacy.

Article

作者: Morello, Aurore ; Quach, Hue Tu ; Zeltsman, Masha ; Adusumilli, Prasad S ; De Biasi, Andreas ; Gomez, Daniel R ; Byun, Alexander J ; Bellis, Rebecca Y ; Mittal, Vivek ; Amador-Molina, Alfredo ; Xiong, Yuquan ; Saini, Jasmeen ; Mayor, Marissa ; Banerjee, Srijita ; Skovgard, Matthew S ; Jones, David R ; Bai, Yang ; Rimner, Andreas ; Chintala, Navin K ; Vista, William-Ray ; Villena-Vargas, Jonathan

Infiltration of tumor by T cells is a prerequisite for successful immunotherapy of solid tumors. In this study, we investigate the influence of tumor-targeted radiation on chimeric antigen receptor (CAR) T-cell therapy tumor infiltration, accumulation, and efficacy in clinically relevant models of pleural mesothelioma and non-small cell lung cancers. We use a nonablative dose of tumor-targeted radiation prior to systemic administration of mesothelin-targeted CAR T cells to assess infiltration, proliferation, antitumor efficacy, and functional persistence of CAR T cells at primary and distant sites of tumor. A tumor-targeted, nonablative dose of radiation promotes early and high infiltration, proliferation, and functional persistence of CAR T cells. Tumor-targeted radiation promotes tumor-chemokine expression and chemokine-receptor expression in infiltrating T cells and results in a subpopulation of higher-intensity CAR-expressing T cells with high coexpression of chemokine receptors that further infiltrate distant sites of disease, enhancing CAR T-cell antitumor efficacy. Enhanced CAR T-cell efficacy is evident in models of both high-mesothelin-expressing mesothelioma and mixed-mesothelin-expressing lung cancer-two thoracic cancers for which radiotherapy is part of the standard of care. Our results strongly suggest that the use of tumor-targeted radiation prior to systemic administration of CAR T cells may substantially improve CAR T-cell therapy efficacy for solid tumors. Building on our observations, we describe a translational strategy of "sandwich" cell therapy for solid tumors that combines sequential metastatic site-targeted radiation and CAR T cells-a regional solution to overcome barriers to systemic delivery of CAR T cells.

2021-06-01·Cancer Research1区 · 医学

Mesothelin-Specific CAR T Cells Target Ovarian Cancer

1区 · 医学

Article

作者: Lehti, Kaisa ; Gultekin, Okan ; He, Rui ; Magalhaes, Isabelle ; Mattsson, Jonas ; Poiret, Thomas ; Carlson, Joseph W. ; Hassan, Moustapha ; Moyano-Galceran, Lidia ; El-Serafi, Ibrahim ; Zhao, Ying ; Schoutrop, Esther

AbstractNew therapeutic options for patients with ovarian cancer are urgently needed. Therefore, we evaluated the efficacy of two second-generation mesothelin (MSLN)-directed CAR T cells in orthotopic mouse models of ovarian cancer. Treatment with CAR T cells expressing an MSLN CAR construct including the CD28 domain (M28z) significantly prolonged survival, but no persistent tumor control was observed. Despite lower response rates, MSLN-4–1BB (MBBz) CAR T cells induced long-term remission in some SKOV3–bearing mice. Tumor-infiltrating M28z and MBBz CAR T cells upregulated PD-1 and LAG3 in an antigen-dependent manner while MSLN+ tumor cells expressed the corresponding ligands (PD-L1 and HLA-DR), demonstrating that coinhibitory pathways impede CAR T-cell persistence in the ovarian tumor microenvironment. Furthermore, profiling plasma soluble factors identified a cluster of M28z- and MBBz-treated mice characterized by elevated T-cell secreted factors that had increased survival, higher CD8+ T-cell tumor infiltration, less exhausted CAR T-cell phenotypes, and increased HLA-DR expression by tumor cells. Altogether, our study demonstrates the therapeutic potential of MSLN-CAR T cells to treat ovarian cancer.Significance:These findings demonstrate that MSLN-directed CAR T cells can provide antitumor immunity against ovarian cancer.

2021-05-04·Expert Opinion on Biological Therapy

Regulatory challenges and considerations for the clinical application of CAR T cell therapy

作者: Kurian, Tony J ; Davila, Marco L ; Bachmeier, Christina A

A review.Chimeric antigen receptor T (CAR T) cell therapy has revolutionized the treatment of relapsed and refractory hematol. malignancies leading to their integration into treatment algorithms.The use of CD19 targeted CAR T cells outside the clin. trial setting following FDA approval has brought to light clin. and regulatory challenges of the therapy.

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