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

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

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

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

2021-04-15·Cureus

A Systematic Review of the Role of Chimeric Antigen Receptor T (CAR-T) Cell Therapy in the Treatment of Solid Tumors

Review

作者: Sardar, Muhammad ; Siddiqui, Raheel S

Chimeric antigen receptor T (CAR-T) cell therapy utilizes patients' own T lymphocytes that are engineered to attack cancer cells. It is Food and Drug Administration (FDA)-approved in various hematological malignancies and currently being evaluated in solid cancers in early phase studies. We did a systematic review consisting of 15 prospective clinical trials (n=159) evaluating CAR-T cells in solid cancers. Early phase trials showed promising response rates in ovarian epithelial cancer (100%), human epidermal growth factor receptor 2 (HER2)-positive sarcoma (67%), epidermal growth factor receptor (EGFR)-positive biliary tract cancer (65%), advanced gastric/pancreatic cancer (82%), hepatocellular carcinoma (67%), and colorectal cancer (70%). The median overall response across all malignancies was 62% (range 17%-100%). Median progression-free survival and overall survival were not reached in most trials. Cytokine release syndrome was seen in only one patient with cholangiocarcinoma who received EGFR-specific CAR-T cell therapy. Although survival data is still not mature, CAR-T cell therapy in solid malignancies did show encouraging response rates and was well-tolerated.

Frontiers in Molecular Medicine

Novel modular chimeric antigen receptor spacer for T cells derived from signal regulatory protein alpha Ig-like domains

Article

作者: Luostarinen, Annu ; Maliniemi, Pilvi ; Ojala, Päivi M ; Monzo, Hector ; Jahan, Farhana ; Schenkwein, Diana ; Ylä-Herttuala, Seppo ; Korhonen, Matti ; Koski, Jan ; Göös, Helka

Background: T cells equipped with chimeric antigen receptors (CAR) have shown remarkable efficacy in targeting B lineage malignancies. Improvement of the CAR structure is needed, however, with a view to developing flexibly modifiable spacers that are inert in interactions with unwanted cells. Specifically, binding to cells carrying receptors for IgG’s crystallizable fragment (FcR), that recognize IgG-derived domains in CARs is to be avoided.Methods: Two novel CARs targeting the CD19 antigen where the IgG1-CH2 and -CH3 domains were replaced with Ig-like domains from signal-regulatory protein α (SIRPα) were designed in silico. An IgG1-based CAR and a CAR lacking both SIRPα and IgG1 domains were used as comparators. The phenotype and memory phenotype of the expanded cells were analyzed by flow cytometry, and CAR T cell activation and cytotoxic efficacy were assessed in co-culture experiments in response to CD19+ target cells. Unwanted interactions with FcR-expressing myeloid cells were interrogated in co-culture assays with THP-1 monocytic cells.Results: T cells carrying the novel SIRPα-based CARs enacted potent in vitro cytotoxicity against CD19 positive B-lineage leukemia cells, comparable to traditional IgG1-based CAR T cells. Co-culture of IgG1-based CAR T cells with FcR-expressing THP-1 monocytic cells led to prominent cell surface expression of CD69 on T cells together with production of Interleukin (IL)-2 and Interferon-γ, and production of IL-1β, indicating activation of the T cells and monocytes, respectively. Longer co-culture led to killing of the monocytes. No signs of T cell nor monocyte activation were detected in co-cultures of SIRPα-based CAR T cells with THP-1 cells. Arming T cells with the SIRPα-based CARs favored differentiation towards CD4+ phenotype during expansion, while the effects on memory phenotype of the T cells were equivalent between the SIRPα- and IgG1-based CARs. In a pilot experiment, T cells modified with one of the SIRPα-based CARs showed dose dependent leukemia cell control.Conclusion: The novel SIRPα based spacers offer a suitable backbone for developing chimeric antigen receptors that evade the off-target binding to FcR while the cells retain a favorable memory phenotype and efficient cytotoxicity, establishing a promising candidate for future in vivo and clinical testing.

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

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