This phase I trial investigates the efficacy and safety of brain-targeting epidermal growth factor receptor chimeric antigen receptor immune cells (EGFRvIII-CAR T cells) in treating patients with leptomeningeal disease from glioblastoma. T cells are part of the immune system and help the body fight malignant tumours. Immune cells can be genetically modified to destroy brain tumor cells in the laboratory. EGFRvIII -CAR T cells are brain tumor specific and can enter and express its genes in immune cells. Administering patients EGFRvIII -CAR T cells may help to recognize and destroy brain tumor cells in patients with leptomeningeal disease from glioblastoma.

开始日期2020-05-15

申办/合作机构

Chembrain Consults LTD

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100 项与 Anti-EGFRvIII CAR-T-cell therapy (Chembrain LTD/University of Oulu) 相关的临床结果

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100 项与 Anti-EGFRvIII CAR-T-cell therapy (Chembrain LTD/University of Oulu) 相关的转化医学

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100 项与 Anti-EGFRvIII CAR-T-cell therapy (Chembrain LTD/University of Oulu) 相关的专利（医药）

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项与 Anti-EGFRvIII CAR-T-cell therapy (Chembrain LTD/University of Oulu) 相关的文献（医药）

2023-03-01·Journal for ImmunoTherapy of Cancer

Anti-VEGF therapy improves EGFR-vIII-CAR-T cell delivery and efficacy in syngeneic glioblastoma models in mice

Article

作者: Datta, Meenal ; Ren, Jun ; Amoozgar, Zohreh ; Jain, Rakesh K ; Duquette, Mark ; Roberge, Sylvie ; Fukumura, Dai ; Lee, Somin ; Dong, Xinyue

Chimeric antigen receptor (CAR)-T cells have revolutionized the treatment of multiple types of hematological malignancies, but have shown limited efficacy in patients with glioblastoma (GBM) or other solid tumors. This may be largely due to the immunosuppressive tumor microenvironment (TME) that compromises CAR-T cells’ delivery and antitumor activity. We previously showed that blocking vascular endothelial growth factor (VEGF) signaling can normalize tumor vessels in murine and human tumors, including GBM, breast, liver, and rectal carcinomas. Moreover, we demonstrated that vascular normalization can improve the delivery of CD8+ T cells and the efficacy of immunotherapy in breast cancer models in mice. In fact, the US FDA (Food and drug administration) has approved seven different combinations of anti-VEGF drugs and immune checkpoint blockers for liver, kidney, lung and endometrial cancers in the past 3 years. Here, we tested the hypothesis that anti-VEGF therapy can improve the delivery and efficacy of CAR-T cells in immunocompetent mice bearing orthotopic GBM tumors. We engineered two syngeneic mouse GBM cell lines (CT2A and GSC005) to express EGFRvIII—one of the most common neoantigens in human GBM—and CAR T cells to recognize EGFRvIII. We found that treatment with the anti-mouse VEGF antibody (B20) improved CAR-T cell infiltration and distribution throughout the GBM TME, delayed tumor growth, and prolonged survival of GBM-bearing mice compared with EGFRvIII-CAR-T cell therapy alone. Our findings provide compelling data and a rationale for clinical evaluation of anti-VEGF agents with CAR T cells for GBM patients.

100 项与 Anti-EGFRvIII CAR-T-cell therapy (Chembrain LTD/University of Oulu) 相关的药物交易

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研发状态

10 条进展最快的记录,

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适应症	最高研发状态	国家/地区	公司	日期
多形性胶质母细胞瘤	临床1期	印度	Chembrain Consults LTD	2020-05-15
多形性胶质母细胞瘤	临床1期	芬兰	Chembrain Consults LTD	2020-05-15
多形性胶质母细胞瘤	临床1期	芬兰	University of Oulu	2020-05-15
多形性胶质母细胞瘤	临床1期	印度	University of Oulu	2020-05-15
脑膜肿瘤	临床1期	芬兰	University of Oulu	2020-05-15
脑膜肿瘤	临床前	芬兰	Chembrain Consults LTD	2020-05-15
脑膜肿瘤	临床前	印度	Chembrain Consults LTD	2020-05-15
脑膜肿瘤	临床前	印度	University of Oulu	2020-05-15