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 B7-H3-CAR-T Cells(Guangdong Zhaotai InVivo Biomedicine) 相关的临床结果

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100 项与 B7-H3-CAR-T Cells(Guangdong Zhaotai InVivo Biomedicine) 相关的转化医学

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100 项与 B7-H3-CAR-T Cells(Guangdong Zhaotai InVivo Biomedicine) 相关的专利（医药）

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项与 B7-H3-CAR-T Cells(Guangdong Zhaotai InVivo Biomedicine) 相关的文献（医药）

2023-08-01·Cancer Letters

A novel microenvironment regulated system CAR-T (MRS.CAR-T) for immunotherapeutic treatment of esophageal squamous carcinoma

Article

作者: Miao, Jinxin ; Zhang, Lufang ; Zhang, Na ; Wang, Yaohe ; Zhao, Yuanyuan ; Hu, Xuanyu ; Wang, Jianyao ; Wang, Jingjing ; Cheng, Zhenguo ; Wang, Lihong ; Zhang, Danhua ; Wang, Xiaosa ; Chard Dunmall, Louisa S ; Zhang, Zifang ; Guo, Haoran ; Zhou, Wenping ; Lemoine, Nicholas R ; Wu, Yangyang

Chimeric antigen receptor T cell immunotherapy has achieved promising therapeutic effects in the treatment of hematological malignancies. However, there are still many obstacles, including on-target off-tumor antigen expression, that prevent successful application to solid tumors. We designed a tumor microenvironment (TME) regulated system chimeric antigen receptor T (MRS.CAR-T) which can only be auto-activated in the solid TME. B7-H3 was selected as the target antigen for esophageal carcinoma. An element comprising a human serum albumin (HSA) binding peptide and a matrix metalloproteases (MMPs) cleavage site was inserted between the 5' terminal signal peptide and single chain fragment variable (scFv) of the CAR skeleton. Upon administration, HSA bound the binding peptide in MRS.B7-H3.CAR-T effectively and promoted proliferation and differentiation into memory cells. MRS.B7-H3.CAR-T was not cytotoxic in normal tissues expressing B7-H3 as the antigen recognition site in the scFv was cloaked by HSA. The anti-tumor function of MRS.B7-H3.CAR-T was recovered once the cleavage site was cleaved by MMPs in the TME. The anti-tumor efficacy associated with MRS.B7-H3.CAR-T cells was improved compared to classic B7-H3.CAR-T cells in vitro and less IFN-γ was released, suggesting a treatment that may induce less extent of cytokine release syndrome-mediated toxicity. In vivo, MRS.B7-H3.CAR-T cells had strong anti-tumor activity and were safe. MRS.CAR-T represents a novel strategy to improve the efficacy and safety of CAR-T therapy in solid tumors.

2023-03-20·European journal of medical research

B7-H3 chimeric antigen receptor-modified T cell shows potential for targeted treatment of acute myeloid leukaemia.

Article

作者: Han, Zhichao ; Fan, Shuangshuang ; An, Gangli ; Zhai, Xiaochen ; Ji, Cheng ; Sheng, Binjie ; Meng, Huimin ; Wang, Tian ; Yang, Lin ; Li, Yafen ; Zhang, Tingting ; You, Fengtao

BACKGROUND AND AIMSChimeric antigen receptor (CAR)-T cell therapy is a novel type of immunotherapy. However, the use of CAR-T cells to treat acute myeloid leukaemia (AML) has limitations. B7-H3 is expressed in several malignancies, including some types of AML cells. However, its expression in normal tissues is low. Therefore, B7-H3 is ideal for targeted AML therapy.MATERIALS AND METHODSFirst, we constructed B7-H3 CAR that can target B7-H3, and then constructed B7-H3-CAR-T cells in vitro, which were co-incubated with six AML cell lines expressing different levels of B7-H3, respectively. The toxicity and cytokines were detected by flow cytometry. In vivo, AML model was established in B-NSG mice to study the toxicity of B7-H3-CAR T on AML cells.RESULTSIn vitro functional tests showed that B7-H3-CAR-T cells were cytotoxic to B7-H3-positive AML tumor cells and had good scavenging effect on B7-H3-expressing AML cell lines, and the cytokine results were consistent. In vivo, B7-H3-CAR-T cells significantly inhibited tumor cell growth in a mouse model of AML, prolonging mouse survival compared with controls.CONCLUSIONB7-H3-CAR-T cells may serve as a novel therapeutic method for the targeted treatment of AML.

100 项与 B7-H3-CAR-T Cells(Guangdong Zhaotai InVivo Biomedicine) 相关的药物交易

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