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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 | Human gamma deltaT cells:candidates for the development of immunotherapeuticstrategies显示文摘 | Beetz S Marischen L Kabelitz D | 2007 | Immunol Res2007，37，： | 1 |
| 4 | Contaminants of medicinal and food herbs with a view to EU regulations显示文摘 | KABELITZ L SIEVERS H | 2004 | Innovations in Food Technology2004，，1： | 1 |
| 5 | Pharmacopoeial monographs for plant extracts 显示文摘 | Brand N Gaedcke F Kabelitz L | 2000 | Pharmeuropa2000，12，2： | 1 |
| 6 | Innate immune functions of human gamma delta T cells显示文摘 | Beetz S Wesch D Marischen L Welte S Oberg HH Kabelitz D | 2008 | Immunobiology2008，213，34： | 1 |
| 7 | Epithelial De- fence by gammadelta T Cells显示文摘 | Kabelitz D Marischen L Oberg HH | 2005 | Int Arch Allergy Immu- nol2005，137，1： | 1 |
| 8 | Reply to:Vitamin C as a promoter of γδ T cells显示文摘Last year,we published a paper in this journal in which we described the effects of vitamin C and its phospho-modified version(phospho-vitamin C,pVC)on the in vitro activation,proliferation,and effector function of humanγδT cells.^(1)We were delighted to see that our study was recently highlighted in a Comment in this journal by Meraviglia and Dieli,2 underscoring the potential interest in using vitamin C to promoteγδT cell activity for use in cancer immunotherapy.Our study was a joint publication with our Chinese collaborators,headed by Prof.Zhinan Yin,with whom we share an interest in exploring the beneficial effects of vitamin C on boosting the cellular immune response.In fact,Yin and colleagues initiated clinical studies on the adoptive transfer of allogeneicγδT cells expanded in the presence of vitamin C into cancer patients.A report of a clinical phase I study demonstrating the safety of allogeneicγδT cell transfer has recently been published in this journal,another collaborative effort of our two groups.^(3) | Léonce Kouakanou Christian Peters Dieter Kabelitz | 2021 | Cellular & Molecular Immunology2021，18，2： | 0 |
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