Mesothelin-CAR-T Cells(Guangdong Zhaotai InVivo Biomedicine)(Mesothelin-CAR-T Cells(Guangdong Zhaotai InVivo Biomedicine)) - 药物靶点：HPK1 x MSLN x PD-1_在研适应症：肺癌_专利_临床

概要

基本信息

药物类型

CAR-T

别名-

靶点

HPK1 x MSLN x PD-1

作用方式

抑制剂

作用机制

HPK1抑制剂(造血祖细胞激酶1抑制剂)、MSLN抑制剂(间皮素抑制剂)、PD-1抑制剂(细胞程序性死亡-1抑制剂)

+ [2]

治疗领域

肿瘤呼吸系统疾病

在研适应症

肺癌

非在研适应症-

原研机构

广东昭泰体内生物医药科技有限公司

在研机构

广东昭泰体内生物医药科技有限公司

非在研机构-

最高研发阶段临床1期

首次获批日期-

最高研发阶段(中国)临床1期

特殊审评-

登录后查看时间轴

关联

1

项与 Mesothelin-CAR-T Cells(Guangdong Zhaotai InVivo Biomedicine) 相关的临床试验

NCT03198052

/ Recruiting临床1期IIT

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

[+2]

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

登录后查看更多信息

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

登录后查看更多信息

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

登录后查看更多信息

11

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

2024-11-22·JCI Insight

Affinity-tuned mesothelin CAR T cells demonstrate enhanced targeting specificity and reduced off-tumor toxicity

Article

作者: Tremblay, Jacqueline M. ; Yang, Yanping ; Tremblay, Jacqueline M ; Babu, Diella S. ; Babu, Diella S ; Alcaina, Yago ; Shoemaker, Charles B. ; Trumper, Sydney J. ; Vedvyas, Yogindra ; Min, Irene M ; Shoemaker, Charles B ; Jin, Moonsoo M ; Jin, Moonsoo M. ; Min, Irene M. ; Trumper, Sydney J

The application of chimeric antigen receptor (CAR) T cell therapy in solid tumors is hindered by life-threatening toxicities resulting from on-target, off-tumor killing of nonmalignant cells that express low levels of the target antigen. Mesothelin (MSLN) has been identified as a target antigen for CAR T cell treatment of mesothelioma, lung, ovarian, and other cancers because of its high expression on tumor cells and limited expression on mesothelial cells. However, fatal off-tumor toxicity of high-affinity MSLN-targeting CAR T cells has been reported in multiple clinical trials. In this study, we constructed CARs using mutant variants of a single-domain nanobody that bind both human and mouse MSLN with a wide range of affinities and examined tumor responses and their toxicities from on-target, off-tumor interactions in mouse models. CAR T cells with low nanomolar affinity (equilibrium dissociation constant, KD) exhibited profound systemic expansion with no apparent infiltration into the tumor. With a gradual reduction of CAR affinity toward the micromolar KD, the expansion of CAR T cells became more restricted to tumors. Our preclinical studies demonstrated that high-affinity MSLN CARs were associated with fatal on-target, off-tumor toxicity and that affinity-tuned CARs rendered T cells more selective for MSLN-high tumors.

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 ; Xing, Shujun ; Wang, Shuhang ; Zhao, Guo

2024-05-01·Clinical Cancer Research

Mesothelin CAR T Cells Secreting Anti-FAP/Anti-CD3 Molecules Efficiently Target Pancreatic Adenocarcinoma and its Stroma

Article

作者: Silva, Harrison ; Fu, Juan ; Korell, Felix ; Guinn, Samantha ; Boland, Genevieve M. ; Sun, Yi ; Scarfò, Irene ; Grauwet, Korneel ; Leick, Mark B. ; Kuo, Adam ; Armstrong, Todd D. ; Zimmerman, Jacquelyn W. ; Almazan, Antonio J. ; Song, Yuhui ; Zhang, Rui ; Zheng, Lei ; Zhu, Qingfeng ; Larson, Rebecca C. ; Bailey, Stefanie R. ; Jan, Max ; Burkhart, Richard A. ; Bouffard, Amanda A. ; Birocchi, Filippo ; Kienka, Tamina ; Kann, Michael C. ; Jaffee, Elizabeth M. ; Schmidts, Andrea ; Salas-Benito, Diego ; Montero Llopis, Paula ; Anekal, Praju Vikas ; Maus, Marcela V. ; Liss, Andrew S. ; Choi, Bryan D. ; Berger, Trisha R. ; Xu, Katherine H. ; Ting, David T. ; Nieman, Linda T. ; Jenkins, Russell W. ; Wehrli, Marc

AbstractPurpose:Targeting solid tumors with chimeric antigen receptor (CAR) T cells remains challenging due to heterogenous target antigen expression, antigen escape, and the immunosuppressive tumor microenvironment (TME). Pancreatic cancer is characterized by a thick stroma generated by cancer-associated fibroblasts (CAF), which may contribute to the limited efficacy of mesothelin-directed CAR T cells in early-phase clinical trials. To provide a more favorable TME for CAR T cells to target pancreatic ductal adenocarcinoma (PDAC), we generated T cells with an antimesothelin CAR and a secreted T-cell–engaging molecule (TEAM) that targets CAF through fibroblast activation protein (FAP) and engages T cells through CD3 (termed mesoFAP CAR-TEAM cells).Experimental Design:Using a suite of in vitro, in vivo, and ex vivo patient-derived models containing cancer cells and CAF, we examined the ability of mesoFAP CAR-TEAM cells to target PDAC cells and CAF within the TME. We developed and used patient-derived ex vivo models, including patient-derived organoids with patient-matched CAF and patient-derived organotypic tumor spheroids.Results:We demonstrated specific and significant binding of the TEAM to its respective antigens (CD3 and FAP) when released from mesothelin-targeting CAR T cells, leading to T-cell activation and cytotoxicity of the target cell. MesoFAP CAR-TEAM cells were superior in eliminating PDAC and CAF compared with T cells engineered to target either antigen alone in our ex vivo patient-derived models and in mouse models of PDAC with primary or metastatic liver tumors.Conclusions:CAR-TEAM cells enable modification of tumor stroma, leading to increased elimination of PDAC tumors. This approach represents a promising treatment option for pancreatic cancer.

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

登录后查看更多信息