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GD2 chimeric antigen receptor modified T cells in synergy with sub-toxic level of doxorubicin targeting osteosarcomas.

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机构： [1]Department of Molecular Genetics and Microbiology, University of Florida, Gainesville, FL 32610, USA [2]Center of Research Excellence on Therapeutic Proteins and Antibody Engineering, Department of Parasitology, Bangkok, Thailand [3]Siriraj Center of Research Excellence for Cancer Immunotherapy, Siriraj Medical Research Center, Faculty of Medicine, Siriraj Hospital, Mahidol University, Bangkok, Thailand [4]Division of Pediatric Hematology-Oncology, Department of Pediatrics [5]Brain Tumor Immunotherapy Program, Department of Neurosurgery, [6]Department of Small Animal Clinical Sciences, University of Florida, [7]University of Electronic Science and Technology of China, Sichuan, China [8]Shenzhen Geno-Immune Medical Institute, Shenzhen, China.

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关键词： GD2 sarcoma chimeric antigen receptor PD-L1 PD1 doxorubicin

摘要：

Since the prognosis for children with high-risk osteosarcoma (OS) remains suboptimal despite intensive multi-modality therapies, there is a clear and urgent need for the development of targeted therapeutics against these refractory malignancies. Chimeric antigen receptor (CAR) modified T cells can meet this need by utilizing the immune system's potent cytotoxic mechanisms against tumor specific antigen targets with exquisite specificity. Since OS highly expresses the GD2 antigen, a viable immunotherapeutic target, we sought to assess if CAR modified T cells targeting GD2 could induce cytotoxicity against OS tumor cells. We demonstrated that the GD2 CAR modified T cells were highly efficacious for inducing OS tumor cell death. Interestingly, the OS cells were induced to up-regulate expression of PD-L1 upon interaction with GD2 CAR modified T cells, and the specific interaction induced CAR T cells to overexpress the exhaustion marker PD-1 along with increased CAR T cell apoptosis. To further potentiate CAR T cell killing activity against OS, we demonstrated that suboptimal chemotherapeutic treatment with doxorubicin can synergize with CAR T cells to effectively kill OS tumor cells. AJCR Copyright © 2020.

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出版当年[2020]版：

大类 | 2 区医学

小类 | 3 区肿瘤学

最新[2023]版：

大类 | 3 区医学

小类 | 3 区肿瘤学

第一作者：

第一作者机构： [1]Department of Molecular Genetics and Microbiology, University of Florida, Gainesville, FL 32610, USA [2]Center of Research Excellence on Therapeutic Proteins and Antibody Engineering, Department of Parasitology, Bangkok, Thailand

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通讯作者：

通讯机构： [1]Department of Molecular Genetics and Microbiology, University of Florida, Gainesville, FL 32610, USA [7]University of Electronic Science and Technology of China, Sichuan, China [8]Shenzhen Geno-Immune Medical Institute, Shenzhen, China. [*1]Department of Molecular Genetics and Microbiology, University of Florida, Gainesville, FL 32610, USA.

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