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| 1 | Chimeric antigen receptor-modified T cells for the immunotherapy of patients with EGFR-expressing advanced relapsed/refractory non-small cell lung cancer显示文摘The successes achieved by chimeric antigen receptor-modified T(CAR-T) cells in hematological malignancies raised the possibility of their use in non-small lung cancer(NSCLC). In this phase I clinical study(NCT01869166), patients with epidermal growth factor receptor(EGFR)-positive(>50% expression), relapsed/refractory NSCLC received escalating doses of EGFR-targeted CAR-T cell infusions. The EGFR-targeted CAR-T cells were generated from peripheral blood after a 10 to 13-day in vitro expansion. Serum cytokines in peripheral blood and copy numbers of CAR-EGFR transgene in peripheral blood and in tissue biopsy were monitored periodically. Clinical responses were evaluated with RECIST1.1 and immune-related response criteria, and adverse events were graded with CTCAE 4.0. The EGFR-targeted CAR-T cell infusions were well-tolerated without severe toxicity. Of 11 evaluable patients, two patients obtained partial response and five had stable disease for two to eight months. The median dose of transfused CAR+ T cells was 0.97×10~7 cells kg^(-1)(interquartile range(IQR), 0.45 to 1.09×10~7 cells kg^(-1)). Pathological eradication of EGFR positive tumor cells after EGFR-targeted CAR-T cell treatment can be observed in tumor biopsies, along with the CAR-EGFR gene detected in tumor-infiltrating T cells in all four biopsied patients. The EGFR-targeted CAR-T cell therapy is safe and feasible for EGFR-positive advanced relapsed/refractory NSCLC. | Kaichao Feng Yelei Guo Hanren Dai Yao Wang Xiang Li Hejin Jia Weidong Han | 2016 | Science China(Life Sciences)2016，59，5： | 62 |
| 2 | Phase I study of chimeric antigen receptor modified T cells in treating HER2-positive advanced biliary tract cancers and pancreatic cancers显示文摘 | Kaichao Feng Yang Liu Yelei Guo Jingdan Qiu Zhiqiang Wu Hanren Dai Qingming Yang Yao Wang Weidong Han1,3 | 2018 | Protein & Cell2018，9，10： | 37 |
| 3 | Manganese is critical for antitumor immune responses via cGAS-STING and improves the efficacy of clinical immunotherapy显示文摘CD8^+T cell-mediated cancer clearance is often suppressed by the interaction between inhibitory molecules like PD-1 and PD-L1,an interaction acts like brakes to prevent T cell overreaction under normal conditions but is exploited by tumor cells to escape the immune surveillance.Immune checkpoint inhibitors have revolutionized cancer therapeutics by removing such brakes.Unfortunately,only a minority of cancer patients respond to immunotherapies presumably due to inadequate immunity.Antitumor immunity depends on the activation of the cGAS-STING pathway,as STING-deficient mice fail to stimulate tumor-infiltrating dendritic cells(DCs)to activate CD8^+T cells.STING agonists also enhance natural killer(NK)cells to mediate the clearance of CD8^+T cell-resistant tumors.Therefore STING agonists have been intensively sought after.We previously discovered that manganese(Mn)is indispensable for the host defense against cytosolic dsDNA by activating cGAS-STING.Here we report that Mn is also essential in innate immune sensing of tumors and enhances adaptive immune responses against tumors.Mn-insufficient mice had significantly enhanced tumor growth and metastasis,with greatly reduced tumor-infiltrating CD8^+T cells.Mechanically,Mn^2+promoted DC and macrophage maturation and tumor-specific antigen presentation,augmented CD8^+T cell differentiation,activation and NK cell activation,and increased memory CD8^+T cells.Combining Mn^2+with immune checkpoint inhibition synergistically boosted antitumor efficacies and reduced the anti-PD-1 antibody dosage required in mice.Importantly,a completed phase 1 clinical trial with the combined regimen of Mn^2+and anti-PD-1 antibody showed promising efficacy,exhibiting type I IFN induction,manageable safety and revived responses to immunotherapy in most patients with advanced metastatic solid tumors.We propose that this combination strategy warrants further clinical translation. | Mengze Lv Meixia Chen Rui Zhang Wen Zhang Chenguang Wang Yan Zhang Xiaoming Wei Yukun Guan Jiejie Liu Kaichao Feng Miao Jing Xurui Wang Yun-Cai Liu Qian Mei Weidong Han Zhengfan Jiang | 2020 | Cell Research2020，30，11： | 27 |
| 4 | Effectiveness of Inactivated COVID-19 Vaccines Against Symptomatic,Pneumonia,and Severe Disease Caused by the Delta Variant:Real World Study and Evidence—China,2021显示文摘Summary What is already known about this topic?Effectiveness of China’s 2 inactivated vaccines(BBIBPCorV and CoronaVac)against pre-Delta severe acute respiratory syndrome coronavirus-2(SARS-CoV-2)variants ranged from 47%to over 90%,depending on the clinical endpoint,and with greater effectiveness against more severe coronavirus disease 2019(COVID-19).During an outbreak in Guangdong,inactivated vaccine effectiveness(VE)against the Delta variant was 70%for symptomatic infection and 100%for severe COVID-19.However,separate or combined VE estimates for the two inactivated vaccines against Delta are not available.What is added by this report?In an outbreak that started in a hospital,VEs of completed primary vaccination with inactivated COVID-19 vaccines against symptomatic COVID-19,COVID-19 pneumonia,and severe COVID-19 caused by the Delta variant were 51%,61%,and 82%.Completed primary vaccination reduced the risk of progressing from mild to moderate or severe COVID-19 by 74%.VE estimates for BBIBP-CorV and CoronaVac or combined vaccination were similar,and partial vaccination was ineffective.What are the implications for public health practice?Completed primary vaccination with either of the 2 inactivated COVID-19 vaccines reduces risk of symptomatic COVID-19,COVID-19 pneumonia,and severe COVID-19 caused by the Delta variant.Completion of the completed primary vaccination with two doses is necessary for protection from Delta. | Dan Wu Yanyang Zhang Lin Tang Fuzhen Wang Ying Ye Chao Ma Hui Zheng Wenzhou Yu Lei Cao Yifan Song Abuduwaili Reyimu Xiaoxiao Zhang Haifeng Wang Yifei Nie Mingxia Lu Muge Qi Jun Li Ruolin Wang Kaichao Yang Changshuang Wang Lawrence Everett Rodewald Geroge Fu Gao Zhijie An Zundong Yin | 2022 | China CDC weekly2022，4，4： | 7 |
| 5 | Phase I study of CAR-T cells with PD-1 and TCR disruption in mesothelin-positive solid tumors显示文摘Programmed cell death protein-1(PD-1)-mediated immunosuppression has been proposed to contribute to the limited clinical efficacy of chimeric antigen receptor T(CAR-T)cells in solid tumors.We generated PD-1 and T cell receptor(TCR)deficient mesothelin-specific CAR-T(MPTK-CAR-T)cells using CRISPR-Cas9 technology and evaluated them in a dose-escalation study.A total of 15 patients received one or more infusions of MPTK-CAR-T cells without prior lymphodepletion.No dose-limiting toxicity or unexpected adverse events were observed in any of the 15 patients.The best overall response was stable disease(2/15 patients).Circulating MPTK-CAR-T cells peaked at days 7–14 and became undetectable beyond 1 month.TCR-positive CAR-T cells rather than TCR-negative CAR-T cells were predominantly detected in effusion or peripheral blood from three patients after infusion.We further confirmed the reduced persistence of TCR-deficient CAR-T cells in animal models.Our results establish the preliminary feasibility and safety of CRISPR-engineered CAR-T cells with PD-1 disruption and suggest that the natural TCR plays an important role in the persistence of CAR-T cells when treating solid tumors. | Zhenguang Wang Na Li Kaichao Feng Meixia Chen Yan Zhang Yang Liu Qingming Yang Jing Nie Na Tang Xingying Zhang Chen Cheng Lianjun Shen Jiaping He Xun Ye Wei Cao Haoyi Wang Weidong Han | 2021 | Cellular & Molecular Immunology2021，18，9： | 7 |
| 6 | An analytical biomarker for treatment of patients with recurrent B-ALL after remission induced by infusion of anti-CD19 chimeric antigen receptor T(CAR-T) cells显示文摘Anti-CD19 chimeric antigen receptor-modified T(CAR-T-19) cells have emerged as a powerful targeted immunotherapy for B-cell lineage acute lymphoblastic leukemia with a remarkable clinical response in recent trials. Nonetheless, few data are available on the subsequent clinical monitoring and treatment of the patients, especially those with disease recurrence after CAR-T-19 cell infusion. Here, we analyzed three patients who survived after our phase I clinical trial and who were studied by means of biomarkers reflecting persistence of CAR-T-19 cells in vivo and predictive factors directing further treatment. One patient achieved 9-week sustained complete remission and subsequently received an allogeneic hematopoietic stem cell transplant. Another patient who showed relapse after 20 weeks without detectable leukemia in the cerebrospinal fluid after CAR-T-19 cell treatment was able to achieve a morphological remission under the influence of stand-alone low-dose chemotherapeutic agents. The third patient gradually developed extensive extramedullary involvement in tissues with scarce immune-cell infiltration during a long period of hematopoietic remission after CAR-T-19 cell therapy. Long-term and discontinuous increases in serum cytokines(mainly interleukin 6 and C-reactive protein) were identified in two patients(Nos. 1 and 6) even though only a low copy number of CAR molecules could be detected in their peripheral blood. This finding was suggestive of persistent functional activity of CAR-T-19 cells. Combined analyses of laboratory biomarkers with their clinical manifestations before and after salvage treatment showed that the persistent immunosurveillance mediated by CAR-T-19 cells would inevitably potentiate the leukemia-killing effectiveness of subsequent chemotherapy in patients who showed relapse after CAR-T-19-induced remission. | Yajing Zhang Wenying Zhang Hanren Dai Yao Wang Fengxia Shi Chunmeng Wang Yelei Guo Yang Liu Meixia Chen Kaichao Feng Yan Zhang Chuanjie Liu Qingming Yang Suxia Li Weidong Han | 2016 | Science China(Life Sciences)2016，59，4： | 6 |
| 7 | Targeting cancer stem cells by using chimeric antigen receptor-modified T cells: a potential and curable approach for cancer treatment显示文摘 | Yelei Guo Kaichao Feng Yao Wang Weidong Han | 2018 | Protein & Cell2018，9，6： | 3 |
| 8 | Dietary supplementation with 2-hydroxy-4-methyl(thio)butanoic acid and DL-methionine improves productive performance,egg quality and redox status of commercial laying ducks显示文摘This experiment aimed to study the effects of supplemental methionine sources,2-hydroxy-4 methyl(thio)butanoic acid(HMTBa)and DL-Methionine(DL-Met),on productive performance,egg quality,and redox status of laying ducks.A total of 792 healthy 25-wk-old Longyan laying ducks with similar body weights were randomly allotted to 11 treatment groups.Each treatment group had 6 replicates of 12 ducks.The trial lasted for 16 wk.Ducks were fed a basal deficient diet(Met:0.24%;Met+Cys:0.51%)or supplemented with DL-Met or HMTBa at 0.05%,0.12%,0.19%,0.26%,and 0.33%of diet,respectively.Compared with the basal diet,supplementation with either DL-Met or HMTBa increased the average egg weight,egg mass,and decreased feed to egg ratio during the whole trial period(P<0.05).Albumen weight and its ratio to total egg weight were increased,but yolk and shell ratio,albumen height,Haugh unit and shell breaking strength were decreased(P<0.05).Dietary DL-Met or HMTBa supplementation increased taurine,methionine,leucine,tryptophan and arginine content,and decreased serine and lysine content in plasma(P<0.05).The redox status of laying ducks was improved by enhancing the glutathione peroxidase and catalase activities,glutathione content and its ratio relative to glutathione(oxidized)content and decreasing malondialdehyde content and increasing mRNA expression of superoxide dismutase-1,glutathione peroxidase-1,hemeoxygenase-1 and nuclear factor-like 2 in liver and ileum with the supplementation of DL-Met or HMTBa(P<0.05).Liver health status measured by average area proportion lipid droplet was improved with supplementation of DL-Met or HMTBa(P<0.05).Villus height and villus height to crypt depth ratio in the ileum and the ileal gene expression of tight junction protein and occludin were increased with DL-Met or HMTBa supplementation(P<0.05).Taken together,these results suggested that the efficacy of dietary supplementation of HMTBa was similar to DL-Met,and it ranged from 98%to 100%for productive performance and egg albumen ratio in laying ducks(25 to 41 wk). | Yanan Zhang Zhiwei Zhuang Tahir Mahmood Yves Mercier Yongyan Jin Xuebing Huang Kaichao Li Shuang Wang Weiguang Xia Shenglin Wang Miao Yu Wei Chen Chuntian Zheng | 2023 | Animal Nutrition2023，，3： | 1 |
| 9 | Efficiency and side effects of anti-CD38 CAR T cells in an adult patient with relapsed B-ALL after failure of bi-specific CD19/CD22 CAR T cell treatment显示文摘(CAR)T cells and immune checkpoint blockade therapies has shown remarkable outcomes in the field of cancer treatment.1,2 In particular,great success has been achieved in B cell acute lymphocytic leukemia(B-ALL)treated with anti-CD19 CAR T cells.2 However,the loss,mutation,and reduced expression of CD19 are crucial causes for the failure of CAR T cell treatment in leukemia patients.3,4 CD38,a 45-kDa type II glycoprotein,is detectable in BALL,and several studies have indicated the efficacy and safety of CD38 monoclonal antibodies in clinical applications,suggesting that CD38 represents a suitable therapeutic target for the treatment of B-ALL.5,6 In addition,we developed a CAR against CD38,and our preclinical study indicated that anti-CD38 CAR T(CAR T-38)cells could specifically lyse CD38-positive tumor cells.7 Herein,we present the anti-leukemia ability of CAR T-38 cells in an adult relapsed B-ALL patient after failure of bi-specific CD19/CD22 CAR T cell treatment,and this administration of CAR T-38 cells was accompanied by the occurrence of target-mediated toxicities and severe and uncontrollable cytokine release syndrome(CRS). | Yelei Guo Kaichao Feng Chuan Tong Hejin Jia Yang Liu Yao Wang Dongdong Ti Qingming Yang Zhiqiang Wu Weidong Han | 2020 | Cellular & Molecular Immunology2020，17，4： | 1 |
| 10 | Towards the selectivity distinction of phenol hydrogenation on noble metal catalysts显示文摘Selective hydrogenation of phenol to cyclohexanone is intriguing in chemical industry.Though a few catalysts with promising performances have been developed in recent years,the basic principle for catalyst design is still missing owing to the unclear catalytic mechanism.This work tries to unravel the mechanism of phenol hydro-genation and the reasons causing the selectivity discrepancy on noble metal catalysts under mild conditions.Results show that different reaction pathways always firstly converge to the formation of cyclohexanone under mild conditions.The selectivity discrepancy mainly depends on the activity for cyclohexanone sequential hy-drogenation,in which two factors are found to be responsible,i.e.the hydrogenation energy barrier and the competitive chemisorption between phenol and cyclohexanone,if the specific co-catalyzing effect of H 2 O on Ru is not considered.Based on the above results,a quantitative descriptor,E b(one/pl)/E a,in which E a can be further correlated to the d band center of the noble metal catalyst,is proposed by the first time to roughly evaluate and predict the selectivity to cyclohexanone for catalyst screening. | Shanjun Mao Zhe Wang Zhirong Chen Kejun Wu Kaichao Zhang Qichuan Li Huihuan Yan Guofeng Lü Guodong Huang Yong Wang | 2023 | Nano Materials Science2023，5，1： | 0 |
| 11 | Effects of Seed Soaking with Paclobutrazol on Early Tillering and Endogenous Hormone Contents of Sugarcane Seedlings显示文摘[Objective] The paper was to explore the effect of seed soaking with paclobutrazol( PP333) on early tillering and endogenous hormone content of sugarcane seedlings.[Method] With the sugarcane variety ROC22 as the experimental material,seeds were soaked in different concentrations of PP333. The number and growth of tiller were investigated,and the contents of endogenous hormones IAA,CTK,ABA and GA3 at two-leaf,four-leaf and six-leaf stages of sugarcane seedlings were measured,to study the effects of seed soaking with PP333 on early tillering and endogenous hormone contents of sugarcane seedlings.[Result] Seed soaking with PP333 could effectively improve and advance tillering occurrence of sugarcane seedlings. The suitable PP333 concentration for sugarcane tillering occurrence,growth and development was 50 mg/L. Seed soaking with PP333 significantly increased the CTK and ABA contents in leaves of sugarcane seedlings,and decreased IAA and GA3 contents. [Conclusion]The paper will provide a theoretical basis for application of PP333 in sugarcane production. | Liu Junxian Li Song Tan Fang Xiong Faqian Wang Xiaoman Guo Wenchan Liu Xin He Yibo Wu Kaichao Liu Limin Liu Hongjian Yu Kunxing Dan Ming Lu Manman | 2017 | Plant Diseases and Pests2017，8，1： | 0 |
| 12 | Dual Effects of Interfacial Interaction and Geometric Constraints on Structural Formation of Poly(butylene terephthalate)Nanorods显示文摘When the size of the material is smaller than the size of the molecular chain,new nanostructures can be formed by crystallizing polymers in nanoporous alumina.However,the effect of pore wall and geometric constraints on polymer nanostructures remains unclear.In this study,we demonstrate three new restricted nanostructures{upright-,flat-and tilting-ring}in polybutylene terephthalate(PBT)nanorods prepared from nanoporous alumina.The dual effects of geometrical constraints and interfacial interactions on the formation of PBT nanostructures were investigated for the first time by using X-ray diffraction and Cerius^(2) modeling packages.Under weak constraints,the interaction between pore wall and the PBT rings is dominant and the ring plane tends to be parallel to the pore wall and radiate outward to grow the upright-ring crystals.Surprisingly,in strong 2D confinement,a structural formation reversal occurs and geometrical constraints overpower the effect of pore wall.Rings tend to pile up vertically or obliquely along the long axis of the rod,so the flat-and tilting-ring crystals are predominate in the constrained system.In principle,our study of the nanostructure formation based on the geometrical constraints and the pore wall interfacial effects could provide a new route to manipulate the chain assembly at the nanoscale,further improving the performance of polymer nanomaterial. | Kaichao Wang Ziwei Lai Jiaman Huang Haiying Li Ziying Liang Junhao Liang Xing Ouyang Xiaoguang Li Yan Cao | 2022 | Chinese Journal of Polymer Science2022，40，6： | 0 |
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