CAR-T Targeting GPC3, Mesothelin, Claudin18.2, GUCY2C, B7-H3, PSCA, PSMA, MUC1, TGFβ, HER2, Lewis-Y, AXL, or EGFR for Immunotherapy of Lung Cancer: Phase I Clinical Trial

The third generation of CAR-T cells that target GPC3, Mesothelin, Claudin18.2, GUCY2C, B7-H3, PSCA, PSMA, MUC1, TGFβ, HER2, Lewis-Y, AXL, or EGFR have been constructed respectively and their anti-cancer function has been verified by multiple in vitro and in vivo studies.Clinical studies will be performed to test the anti-cancer function of the these individual or combination of the CAR-T cells for immunotherapy of human cancer patients with GPC3, Mesothelin, Claudin18.2, GUCY2C, B7-H3, PSCA, PSMA, MUC1, TGFβ, HER2, Lewis-Y, AXL, or EGFR expressions. In this phase I study, the safety, tolerance, and preliminary efficacy of the GPC3/Mesothelin/Claudin18.2/GUCY2C/B7-H3/PSCA/PSMA/MUC1/TGFβ/HER2/Lewis-Y/AXL/EGFR
-CAR-T cell immunotherapy on human cancers will firstly be tested.

开始日期2017-07-01

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-CAR-T Cells(Guangdong Zhaotai InVivo Biomedicine) 相关的临床结果

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100 项与 Mesothelin-CAR-T Cells(Guangdong Zhaotai InVivo Biomedicine) 相关的转化医学

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100 项与 Mesothelin-CAR-T Cells(Guangdong Zhaotai InVivo Biomedicine) 相关的专利（医药）

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项与 Mesothelin-CAR-T Cells(Guangdong Zhaotai InVivo Biomedicine) 相关的文献（医药）

2024-08-01·Pharmacological Research

Commentary on “Mesothelin CAR-T cells expressing tumor-targeted immunocytokine IL-12 yield durable efficacy and fewer side effects”

Letter

作者: Wang, Yuning ; Li, Ning ; Wang, Shuhang ; Xing, Shujun ; Zhao, Guo

2024-05-20·Zhongguo fei ai za zhi = Chinese journal of lung cancer

[Advances in Targeted Therapy for Malignant Pleural Mesothelioma].

Review

作者: Fu, Fen ; Zhang, Yang ; Shen, Hong

【中文题目：恶性胸膜间皮瘤靶向治疗的研究进展】【中文摘要：恶性胸膜间皮瘤（malignant pleural mesothelioma, MPM）是侵袭性极强的罕见胸膜表面恶性肿瘤，危险因素包括吸入石棉、遗传因素、基因突变等。现有的化疗、抗血管生成治疗、免疫治疗的效果均不佳，患者的生存期极短。亟需寻找治疗MPM的潜在靶点，目前发现有基因突变靶点如BRCA1相关蛋白1（BRCA associated protein 1, BAP1）和细胞周期蛋白依赖性激酶抑制剂2A（cyclin-dependent kinase 2A, CDKN2A）等；表观遗传靶点如组蛋白赖氨酸去甲基酶4A［lysine (K)-specific demethylase 4A, KDM4A］和赖氨酸特异性去甲基酶1（lysine-specific demethylase 1, LSD1）等；信号蛋白靶点如葡萄糖调节蛋白78（glucose-regulated protein 78, GRP78）及信号转导和转录激活因子3（signal transducer and activator of transcription 3, STAT3）等。迄今为止，可查询的临床试验有组蛋白甲基转移酶抑制剂Tazemetostat、多聚ADP-核糖聚合酶［poly (ADP-ribose) polymerase, PARP］抑制剂Rucaparib和细胞周期蛋白依赖性激酶4/6（cyclin-dependent kinases 4 and 6, CDK4/6）抑制剂Abemaciclib的II期临床试验，以及靶向间皮素的嵌合抗原受体T细胞免疫疗法（chimeric antigen receptor T-cell immunotherapy, CAR-T）细胞胸腔注射、TEA结构域家族成员（TEA domain family member, TEAD）抑制剂VT3989和IK-930的I期临床试验，显示出一定的临床疗效。 】【中文关键词：恶性胸膜间皮瘤；基因突变；表观遗传；信号蛋白；靶向治疗】.

International Journal of Molecular Sciences

Chimeric Antigen Receptor T Cell Bearing Herpes Virus Entry Mediator Co-Stimulatory Signal Domain Exhibits Exhaustion-Resistant Properties

Article

作者: Masuda, Michiaki ; Imuta, Nagisa ; Nunoya, Jun-ichi

Improving chimeric antigen receptor (CAR)-T cell therapeutic outcomes and expanding its applicability to solid tumors requires further refinement of CAR-T cells. We previously reported that CAR-T cells bearing a herpes virus entry mediator (HVEM)-derived co-stimulatory signal domain (CSSD) (HVEM-CAR-T cells) exhibit superior functions and characteristics. Here, we conducted comparative analyses to evaluate the impact of different CSSDs on CAR-T cell exhaustion. The results indicated that HVEM-CAR-T cells had significantly lower frequencies of exhausted cells and exhibited the highest proliferation rates upon antigenic stimulation. Furthermore, proliferation inhibition by programmed cell death ligand 1 was stronger in CAR-T cells bearing CD28-derived CSSD (CD28-CAR-T cells) whereas it was weaker in HVEM-CAR-T. Additionally, HVEM-CAR-T cells maintained a low exhaustion level even after antigen-dependent proliferation and exhibited potent killing activities, suggesting that HVEM-CAR-T cells might be less prone to early exhaustion. Analysis of CAR localization on the cell surface revealed that CAR formed clusters in CD28-CAR-T cells whereas uniformly distributed in HVEM-CAR-T cells. Analysis of CD3ζ phosphorylation indicated that CAR-dependent tonic signals were strongly sustained in CD28-CAR-T cells whereas they were significantly weaker in HVEM-CAR-T cells. Collectively, these results suggest that the HVEM-derived CSSD is useful for generating CAR-T cells with exhaustion-resistant properties, which could be effective against solid tumors.

100 项与 Mesothelin-CAR-T Cells(Guangdong Zhaotai InVivo Biomedicine) 相关的药物交易

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