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Anti-PD-1 antibody armored γδ T cells enhance anti-tumor efficacy in ovarian cancer

Signal Transduction and Targeted Therapy 2023年第11期8卷 5470-5480页

作者： Yue Wang Jingyi Han Dongdong Wang Menghua Cai Yi Xu Yu Hu Hui Chen Wei He Jianmin Zhang Department of Immunology CAMS Key Laboratory of T-cell and ImmunotherapyInstitute of Basic Medical SciencesChinese Academy of Medical Sciences and School of Basic MedicinePeking Union Medical CollegeState Key Laboratory of Common Mechanism Research for Major DiseasesBeijing 1oooo5China Department of Thoracic Surgery Qilu Hospital of Shandong UniversityJinanShandong 250012China haihe laboratory of cellecosystem Chinese Academy of Medical Sciences&Peking Union Medical College288 Nanjing RoadTianjin 300020China Changzhou Xitaihu Institute for Frontier Technology of Cell Therapy Changzhou 213000China

γδ T cells have the unique ability to detect a wide range of tumors with low mutation burdens,making them attractive candidates for CAR-T-cell *** aβT cells and other immune cells,γδ T cells are superior in MHC non-restriction,selective cell recruitment,and rapid ***,clinical trials have shown limited clinical benefits,and the adoptive transplantation of γδ T cells has often fallen short of *** hypothesized that the limited effectiveness of γδ T cells in eradicating tumor cells may be attributed to the inhibitory tumor microenvironment induced by the suppressive PD-1/PD-L1 ***,we constructed novel armored γδ T cells capable of secreting humanized anti-PD-1 antibodies,referred to as"Lv-PD1-ys T ***-PD1-γδ T cells showed improved proliferation and enhanced cytotoxicity against tumor cells,resulting in augmented therapeutic effects and survival benefits in ovarian tumor-bearing *** engineered cells demonstrated a prolonged in vivo survival of more than 29 days,without any potential for tumorigenicity in immunodeficient NOD/SCID/null *** also found that Lv-PD1-γδ T cells exhibited excellent tolerance and safety in humanized NOD/SCID/null *** attenuated or eliminated immunosuppression and maximized cytotoxicity efficacy by the local secretion of anti-PD1 antibodies in tumors,Lv-PD1-γδ T cells can serve as a promising"off-the-shelf"cell therapy against cancers.

关键词： PD1 attractive sized

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