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| 1 | Allogeneic Vγ9Vδ2 T-cell immunotherapy exhibits promising clinical safety and prolongs the survival of patients with late-stage lung or liver cancer显示文摘Vγ9Vδ2 T cells are promising candidates for cellular tumor immunotherapy.Due to their HLA-independent mode of action,allogeneic Vγ9Vδ2 T cells can be considered for clinical application.To apply allogeneic Vγ9Vδ2 T cells in adoptive immunotherapy,the methodology used to obtain adequate cell numbers with optimal effector function in vitro needs to be optimized,and clinical safety and efficacy also need to be proven.Therefore,we developed a novel formula to improve the expansion of peripheralγδT cells from healthy donors.Then,we used a humanized mouse model to validate the therapeutic efficacy of expandedγδT cells in vivo;furthermore,the expandedγδT cells were adoptively transferred into late-stage liver and lung cancer patients.We found that the expanded cells possessed significantly improved immune effector functions,including proliferation,differentiation,and cancer cell killing,both in vitro and in the humanized mouse model.Furthermore,a phase I clinical trial in 132 late-stage cancer patients with a total of 414 cell infusions unequivocally validated the clinical safety of allogeneic Vγ9Vδ2 T cells.Among these 132 patients,8 liver cancer patients and 10 lung cancer patients who received≥5 cell infusions showed greatly prolonged survival,which preliminarily verified the efficacy of allogeneic Vγ9Vδ2 T-cell therapy.Our clinical studies underscore the safety and efficacy of allogeneic Vγ9Vδ2 T-cell immunotherapy,which will inspire further clinical investigations and eventually benefit cancer patients. | Yan Xu Zheng Xiang Mohammed Alnaggar Léonce Kouakanou Jiawei Li Junyi He Jiashuang Yang Yi Hu Yan Chen Li Lin Jianlei Hao Jingxia Li Jibing Chen Man Li Qingling Wu Christian Peters Qinghua Zhou Jianshuang Li Yingqing Liang Xiaohua Wang Baohui Han Meili Ma Dieter Kabelitz Kecheng Xu Wenwei Tu Yangzhe Wu Zhinan Yin | 2021 | Cellular & Molecular Immunology2021，18，2： | 8 |
| 2 | Vitamin C promotes the proliferation and effector functions of human γδ T cells显示文摘γδT cells are of interest as effector cells for cellular immunotherapy due to their HLA-non-restricted lysis of many different tumor cell types.Potential applications include the adoptive transfer of in vitro-expandedγδT cells.Therefore,it is important to optimize the culture conditions to enable maximal proliferative and functional activity.Vitamin C(L-ascorbic acid)is an essential vitamin with multiple effects on immune cells.It is a cofactor for several enzymes,has antioxidant activity,and is an epigenetic modifier.Here,we investigated the effects of vitamin C(VC)and its more stable derivative,L-ascorbic acid 2-phosphate(pVC),on the proliferation and effector function of humanγδT cells stimulated with zoledronate(ZOL)or synthetic phosphoantigens(pAgs).VC and pVC did not increaseγδT-cell expansion within ZOL-or pAg-stimulated PBMCs,but increased the proliferation of purifiedγδT cells and 14-day-expandedγδT-cell lines in response toγδT-cell-specific pAgs.VC reduced the apoptosis ofγδT cells during primary stimulation.While pVC did not prevent activation-induced death of pAg-restimulatedγδT cells,it enhanced the cell cycle progression and cellular expansion.Furthermore,VC and pVC enhanced cytokine production during primary activation,as well as upon pAg restimulation of 14-day-expandedγδT cells.VC and pVC also increased the oxidative respiration and glycolysis ofγδT cells,but stimulus-dependent differences were observed.The modulatory activity of VC and pVC might help to increase the efficacy ofγδT-cell expansion for adoptive immunotherapy. | Léonce Kouakanou Yan Xu Christian Peters Junyi He Yangzhe Wu Zhinan Yin Dieter Kabelitz | 2020 | Cellular & Molecular Immunology2020，17，5： | 3 |
| 3 | 3efining the nature of human yo T cells: a biographical ketch of the highly empathetic显示文摘 | Shirin Kalyan Dieter Kabelitz | 2013 | Cellular & Molecular Immunology2013，10，1： | 2 |
| 4 | Features and functions of gamma delta T lymphocytes: focus on chemokines and their receptors显示文摘 | Kabelitz D Wesch D | 2003 | Crit Rev Immunol2003，23，56： | 1 |
| 5 | Perspectives of gammad- elta T ceils in tumor immunology显示文摘 | Kabelitz D Wesch D He W | 2007 | Cancer Res2007，67，1： | 1 |
| 6 | Secretory lysosomes and their cargo in T and NK cells 显示文摘 | Lettau M Schmidt H Kabelitz D | 2007 | Immunol Lett2007，108，1： | 1 |
| 7 | The primary response of human γ/δ ^+ T cells to Mycobacterium tuberculosis is restricted to Vγ9-bearing cells显示文摘 | Kabelitz DA Bender T Prospero S | 1991 | J Exp Mcd1991，173，6： | 1 |
| 8 | Lysosome-related effector vesicles in T lymphocytes and NK ceils 显示文摘 | Lettau M Kabelitz D Janssen O | 2015 | Scand J Immunol2015，82，3： | 1 |
| 9 | Human T-cell receptor variable gene segment families显示文摘 | Arden B Clark SP Kabelitz D | 1995 | Immunogenetics1995，42，6： | 1 |
| 10 | Differentiation of resting human peripheral blood y8T cells toward Thl or Th2-phenotype 显示文摘 | Wesch D Glatzel A Kabelitz D | 2001 | Cell Immunol2001，212，2： | 1 |
| 11 | induction of activation-driven death(apotosis) in activated but not resting peripheral blood T cells显示文摘 | Wesselborg S Janssen O Kabelitz D | | 0，，10： | 1 |
| 12 | Human γδT lymphocytes 显示文摘 | Kabelitz D | 1993 | Int Arch Allergy Immunol1993，102，1： | 1 |
| 13 | Graft rejection and transplantion tolerance显示文摘 | Kabelitz D Apeptosi S | | 0，，07： | 1 |
| 14 | Human T-cell receptor variablegene segment families 显示文摘 | Arden B Clark SP Kabelitz D | 1995 | Immunogenetics1995，42，6： | 1 |
| 15 | Mouse T-cell receptor variablegene segment families 显示文摘 | Arden B Clark SP Kabelitz D | 1995 | Immunogenetics1995，42，6： | 1 |
| 16 | Regulation of activation-induced cell death of mature T-lymphocyte populations显示文摘 | Janssen O Sanzenbacher R Kabelitz D | | 0，，： | 1 |
| 17 | Regulation of activation-induced cell death of mature T-lymphocyte populations显示文摘 | Ottmar Janssen Ralf Sanzenbacher Dieter Kabelitz | 2000 | Cell and Tissue Research2000，，1： | 1 |
| 18 | Induction of activation-driven death(apoptosis) in activated but not resting peripheral blood T cells显示文摘 | Wesselborg S Janssen O Kabelitz D | 1993 | The Journal of Immunology1993，150，10： | 1 |
| 19 | A rapidcolorimetric assay for the determination of IL-2 producing helper T cell frequencies 显示文摘 | Heeg K Reimann J Kabelitz D | 1985 | J Immun Methods1985，77，： | 1 |
| 20 | Human T-cell receptor variable gene segment families显示文摘 | Arden B Clark S P Kabelitz D | 1995 | Immunogenetics1995，42，： | 1 |
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