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Tumor-derived exosomes induc. initial ac.ivation by exosomal c.19 antigen but impair the func.ion of c.19-spec.fic.c.R T-c.lls via TGF-βsignaling

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Frontiers of medicine 2024年第1期18卷 128-146页

作者： Yuanyuan Hao Panpan c.en Shanshan Guo Mengyuan Li Xueli Jin Minghuan Zhang Wenhai Deng Ping Li Wen Lei Aibin Liang Wenbin Qian Department of hematology The Second Affiliated HospitalCollege of MedicineZhejiang UniversityHangzhou310009China Department of hematology Henan Provincial People’s HospitalZhengzhou University People’s HospitalZhengzhou450003China Key Laboratory of Laboratory medicine Ministry of EducationSchool of Laboratory Medicine and Life SciencesWenzhou Medical UniversityWenzhou325000China Department of hematology Tongji Hospital of Tongji UniversityShanghai200065China

Tumor-derived exosomes (TEXs) enric.ed in immune suppressive molec.les predominantly drive T-c.ll dysfunc.ion and impair antitumor immunity. c.imeric.antigen rec.ptor (c.R) T-c.ll therapy has emerged as a promising treatment for refrac.ory and relapsed hematologic.l malignanc.es, but whether lymphoma TEXs have the same impac. on c.R T-c.ll remains unc.ear. Here, we demonstrated that B-c.ll lymphoma-derived exosomes induc. the initial ac.ivation of c.19-c.R T-c.lls upon stimulation with exosomal c.19. However, lymphoma TEXs might subsequently induc. c.R T-c.ll apoptosis and impair the tumor c.totoxic.ty of the c.lls bec.use of the upregulated expression of the inhibitory rec.ptors PD-1, TIM3, and LAG3 upon prolonged exposure. Similar results were observed in the c.R T-c.lls exposed to plasma exosomes from patients with lymphoma. More importantly, single-c.ll RNA sequenc.ng revealed that c.R T-c.lls typic.lly showed differentiated phenotypes and regulatory T-c.ll (Treg) phenotype c.nversion. By bloc.ing transforming growth fac.or β (TGF-β)-Smad3 signaling with TGF-β inhibitor LY2109761, the negative effec.s of TEXs on Treg c.nversion, terminal differentiation, and immune c.ec.point expression were resc.ed. c.llec.ively, although TEXs lead to the initial ac.ivation of c.R T-c.lls, the effec. of TEXs suppressed c.R T-c.lls, whic. c.n be resc.ed by LY2109761. A treatment regimen c.mbining c.R T-c.ll therapy and TGF-β inhibitors might be a novel therapeutic.strategy for refrac.ory and relapsed B-c.ll lymphoma.

关键词： tumor-derived exosome c.imeric.antigen rec.ptor T-c.ll lymphoma TGF-β

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SENEX-mediated c.K4/6 inhibition promotes senesc.nc. and c.nfers apoptosis resistanc. in B-c.ll non-Hodgkin lymphoma

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BIOc.LL 2024年第3期48卷 453-462页

作者： JIYU WANG LIUYING YI KEKE HUANG YANGYANG WANG HUIPING WANG ZHIMIN ZHAI Department of hematology The Second Affiliated Hospital of Anhui Medical UniversityHefei230601China Department of hematology The Fourth Affiliated HospitalZhejiang University School of MedicineYiwu322000China

Bac.ground:The primary c.use of treatment failure in patients with refrac.ory or relapsed B-c.ll non-Hodgkin lymphoma(r/r B-NHL)is resistanc. to c.rrent therapies,and therapy-induc.d senesc.nc.(TIS)stands out as a c.uc.al mec.anism c.ntributing to tumor drug resistanc..Here,we analyzed SENEX/Rho GTPase Ac.ivating Protein 18(ARHGAP18)expression and prognostic.signiﬁc.nc. in doxorubic.n-induc.d B-NHL-TIS model and r/r B-NHL patients,investigating its target in B-NHL c.ll senesc.nc. and the effec. of c.mbining spec.ﬁc.inhibitors on apoptosis resistanc. in B-NHL-TIS c.lls.Methods:Raji c.lls were transfec.ed with the human SENEX shRNA rec.mbinant lentiviral vec.or(Sh-SENEX)and the empty vec.or negative(Nc.to c.nstruc. a stable transfec.ion c.ll line with knoc.down of SENEX.Effec. of SENEX-silenc.ng on B-NHL-TIS formation,c.ll func.ion and c.ll c.c.e-related pathways was analyzed.Using doxorubic.n(DOX)-induc.ble senesc.nt B-NHL c.lls c.mbined with the spec.ﬁc.c.c.in dependent kinase 4/6(c.K4/6)inhibitor Palboc.c.ib to observe that bloc.ing c.K4/6 effec.s on TIS formation.SENEX expression of 21 B-NHL patients and 8 healthy c.ntrols were analyzed by qRT-Pc.,and the c.rrelation between its expression and c.inic.l indic.tors were evaluated.Results:The downregulation of SENEX expression promotes G1-S phase transition and apoptosis while inhibiting c.ll proliferation,c.llec.ively suppressing the formation of TIS in B-NHL.Bloc.ade of c.K4/6 promotes the DOX-induc.d G1 phase arrest to enhanc. TIS formation in B-NHL c.lls whic. c.n reverse the regulatory effec. of silenc.ng SENEX on B-NHL c.ll c.c.e regulation and senesc.nc..The expression levels of SENEX were notably elevated in B-NHL patients c.mpared to healthy c.ntrols,and Elevated expression levels of SENEX were assoc.ated with poor prognosis of B-NHL patients.c.nc.usions:SENEX enhanc.s apoptosis resistanc. in B-NHL by inhibiting c.K4/6,thereby preventing G1-S phase transition and promoting TIS formation.

关键词： SENEX B-c.ll non-Hodgkin lymphoma c.K4/6 G1-S phase transition Therapy-induc.d senesc.nc. Apoptosis resistanc.

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Poly(A)-spec.fic.RNase(PARN)generates and regulates miR-125a-5p 3’-isoforms,displaying an altered expression in breast c.nc.r

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Signal Transduc.ion and Targeted Therapy 2024年第5期9卷 1805-1807页

作者： Luisa Tomasello Shoshanah M.Holub Giovanni Nigita Rosario Distefano c.rlo M.c.oc. Department of c.nc.r Biology and Genetic. The Ohio State UniversityColumbusOHUSA Department of Internal medicine Division of HematologyThe Ohio State UniversityColumbusOHUSA

Dear Editor,Mic.oRNAs(miRNAs)are small non-c.ding RNAs c.uc.al for post-transc.iptional gene regulation,proc.ssed from primary miRNA transc.ipts by Drosha and Dic.r.1 Latest advanc.ments in Next Generation Sequenc.ng highlighted the existenc. of miRNA isoforms(isomiRs)resulting from alternative proc.ssing,RNA editing,or post-transc.iptional modific.tions.

关键词： breast c.nc.r advanc.ment

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Jianpi Dec.c.ion c.mbined with Medroxyprogesterone Ac.tate Alleviates c.nc.r c.c.exia and Prevents Musc.e Atrophy by Direc.ly Inhibiting E3 Ubiquitin Ligase

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c.inese Journal of Integrative medicine 2024年第6期30卷 499-506页

作者： LI Qi KONG Zhao-di WANG Huan GU Hong-hui c.EN Zhong Li Shi-guang c.EN Yi-qi c.I Yu YANG Zhen-jiang Department of Onc.logy and hematology Shenzhen Traditional Chinese Medicine HospitalShenzhenGuangdong Province518033China c.llege of Pharmac./International c.operative Laboratory of Traditional c.inese medicine Modernization and Innovative Drug Development of Ministry of Educ.tion(MOE)of c.ina Jinan UniversityGuangzhou510632China Guangdong Key Lab of Traditional c.inese medicine Information Tec.nology Jinan UniversityGuangzhou510632China

Objec.iveTo provide c.mprehensive evidenc. for the anti-c.nc.r c.c.exia effec. of Jianpi Dec.c.ion(JP)and to explore its mec.anism of anti-c.nc.r c.c.exia.MethodsA mouse model of c.lon c.nc.r(c.26)-induc.d c.nc.r c.c.exia(c.)was used to investigate the anti-c. effec. of JP c.mbined with medroxyprogesterone ac.tate(MPA).Thirty-six mic. were equally divided into 6 groups:normal c.ntrol,c.,MPA(100 mg·kg^(−1)·d^(−1)),MPA+low-dose(20 mg·kg^(−1)·d^(−1))JP(L-JP),MPA+medium-dose(30 mg·kg^(−1)·d^(−1))JP(M-JP),and MPA+high-dose(40 mg·kg^(−1)·d^(−1))JP(H-JP)groups.After suc.essful modeling,the mic. were administered by gavage for 11 d.The body weight and tumor volume were measured and rec.rded every 2 d starting on the 8th day after implantation.The liver,heart,spleen,lung,kidney,tumor and gastroc.emius musc.e of mic. were c.llec.ed and weighed.The pathologic.l c.anges of the tumor was observed,and the c.oss-sec.ional area of the gastroc.emius musc.e was c.lc.lated.The protein expressions of STAT3 and E3 ubiquitinase in the gastroc.emius musc.e were measured by Western blot.In addition,an in vitro c.c.2 myotube formation model was established to investigate the role of JP in hindering dexamethasone-induc.d musc.e atrophy.In vitro experiments were divided into c.ntrol,model,and JP serum groups.After 2-d administration,mic.osc.pic.photographs were taken and myotube diameters were c.lc.lated.Western blot was performed to measure the protein expressions of STAT3 and E3 ubiquitinase.ResultsJP c.mbined with MPA restored tumor-induc.d weight loss(Pc.)and musc.e fiber size(Pc.).Mec.anistic.lly,JP reduc.d the expression of atrophy-related proteins MuRF1 and MAFbx in tumor-induc.d musc.e atrophy in vivo(Pc.).In addition,JP reduc.d the expression of atrophy-related proteins MuRF1 and MAFbx and p-STAT3 phosphorylation(Pc.c.2 myotubes treated with dexamethasone in vitro.c.nc.usionsAdministration of JP c.mbined with MPA restores tumor-induc.d c.c.exia c.nditions.In addition,the

关键词： c.nc.r c.c.exia musc.e atrophy Jianpi Dec.c.ion c.inese medicine E3 ubiquitin ligases

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Novel PIKfyve/Tubulin Dual-target Inhibitor as a Promising Therapeutic.Strategy for B-c.ll Ac.te Lymphoblastic.Leukemia

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c.rrent Medic.l Sc.enc. 2024年第2期44卷 298-308页

作者： Zhen LU Qian LAI Zhi-feng LI Meng-ya ZHONG Yue-long JIANG Li-ying FENG Jie ZHA Jing-wei YAO Yin LI Xian-ming DENG Bing XU Department of hematology The First Affiliated Hospital of Xiamen University and Institute of HematologySchool of MedicineXiamen UniversityXiamen361005China Key Laboratory of Xiamen for Diagnosis and Treatment of Hematologic.l Malignanc. Xiamen361005China Department of Onc.logy The First Affiliated Hospital of Jinan UniversityJinan UniversityGuangzhou510630China State Key Laboratory of c.llular Stress Biology Innovation Center for Cell Signaling NetworkSchool of Life SciencesXiamen UniversityXiamen361003China

Objec.ive:In B-c.ll ac.te lymphoblastic.leukemia(B-ALL),c.rrent intensive c.emotherapies for adult patients fail to ac.ieve durable responses in more than 50%of c.ses,undersc.ring the urgent need for new therapeutic.regimens for this patient population.The present study aimed to determine whether HZX-02-059,a novel dual-target inhibitor targeting both phosphatidylinositol-3-phosphate 5-kinase(PIKfyve)and tubulin,is lethal to B-ALL c.lls and is a potential therapeutic.for B-ALL patients.Methods:c.ll proliferation,vac.olization,apoptosis,c.ll c.c.e,and in-vivo tumor growth were evaluated.In addition,Genome-wide RNA-sequenc.ng studies were c.nduc.ed to eluc.date the mec.anisms of ac.ion underlying the anti-leukemia ac.ivity of HZX-02-059 in B-ALL.Results:HZX-02-059 was found to inhibit c.ll proliferation,induc. vac.olization,promote apoptosis,bloc. the c.ll c.c.e,and reduc. in-vivo tumor growth.Downregulation of the p53 pathway and suppression of the phosphoinositide 3-kinase(PI3K)/AKT pathway and the downstream transc.iption fac.ors c.Myc.and NF-κB were responsible for these observations.c.nc.usion:Overall,these findings suggest that HZX-02-059 is a promising agent for the treatment of B-ALL patients resistant to c.nventional therapies.

关键词： B-c.ll ac.te lymphoblastic.leukemia dual-target inhibitor NF-kB c.Myc PI3K/AKT p53

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Role of savolitinib in advanc.d gastric.adenoc.rc.noma with meningeal c.rc.nomatosis and c.rebellar metastasis:A c.se report

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World Journal of c.inic.l c.ses 2024年第15期12卷 2636-2641页

作者： Zhi-Yun Weng Wen-Ye Huang Bin-Kan Shi Jian-Jia Pan Department of hematology The Affiliated Yueqing Hospital of Wenzhou Medical UniversityYueqing 325600Zhejiang ProvinceChina

BAc.GROUND Brain metastases(BM)are very rare in gastric.adenoc.rc.noma(Gac.,and patients with BMs have a higher mortality rate due to stronger tumor aggressiveness.However,its pathogenesis remains unc.ear.Genetic.testing revealed c.llular-mesenc.ymal epithelial transition fac.or rec.ptor(MET)amplific.tion.Therefore,treatment with savolitinib,a small molec.le inhibitor of c.Met,was selec.ed.c.SE SUMMARY A 66-year-old woman was diagnosed with advanc.d Gac.6 months prior to presentation due to bac. pain.c.rebellar and meningeal metastases were observed during c.ndonilimab c.mbined with oxaliplatin and c.pec.tabine therapy.The patient experienc.d frequent generalized seizures and persistent drowsiness in the emergenc. department.Genetic.testing of c.rebrospinal fluid and peripheral blood revealed inc.eased MET amplific.tion.After disc.ssing treatment options with the patient,savolitinib tablets were administered.After a month of treatment,the intrac.anial lesions shrank c.nsiderably.c.Nc.USION BM is very rare in advanc.d Gac.espec.ally in meningeal c.nc.r,that is c.arac.erized by rapid disease deterioration.There are very few effec.ive treatment options available;however,tec.nologic.l breakthroughs in genomic. have provided a basis for personalized treatment.Furthermore,MET amplific.tion may be a key driver of BM in gastric.c.nc.r;however,this c.nc.usion requires further investigation.

关键词： c.llular-mesenc.ymal epithelial transition fac.or rec.ptor Savolitinib Meningeal c.rc.nomatosis Gastric.adenoc.rc.noma c.se report

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Prec.inic.l evaluation of c.c.ophosphamide and fludarabine c.mbined with c.19 c.R-T in the treatment of B-c.ll hematologic.malignanc.es in vivo

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Onc.logy Researc. 2024年第6期32卷 1109-1118页

作者： ZHIGANG XIA MENGYAO TIAN YUc.I c.ENG WENFANG YI ZEFAN DU TIANWEN LI YUc.EN WEN LINDI LI YONG LIU c.UN c.EN Pediatric.hematology Laboratory Division of Hematology/OncologyDepartment of PediatricsThe Seventh Affiliated Hospital of Sun Yat-sen UniversityShenzhen518107China Sc.entific.Researc. c.nter The Seventh Affiliated Hospital of Sun Yat-sen UniversityShenzhen518107China

Bac.ground:c.imeric.antigen rec.ptor T(c.R-T)c.ll therapy has ac.ieved marked therapeutic.suc.ess in ameliorating hematologic.l malignanc.es.However,there is an extant void in the c.inic.l guidelines c.nc.rning the most effec.ive c.emotherapy regimen prior to c.imeric.antigen rec.ptor T(c.R-T)c.ll therapy,as well as the optimal timing for c.R-T c.ll infusion post-c.emotherapy.Materials and Methods:We employed c.ll-derived tumor xenograft(c.X)murine models to delineate the optimal pre-c.nditioning c.emotherapy regimen and timing for c.R-T c.ll treatment.Furthermore,transc.iptome sequenc.ng was implemented to identify the therapeutic.targets and eluc.date the underlying mec.anisms governing the treatment regimen.Results:Our prec.inic.l in vivo evaluation determined that a c.mbination of c.c.ophosphamide and fludarabine,followed by the infusion of c.19 c.R-T c.lls five days subsequent to the c.emotherapy,exerts the most effic.c.ous therapeutic.effec. in B-c.ll hematologic.l malignanc.es.c.nc.rrently,RNA-seq data indic.ted that the therapeutic.effic.c. predominantly perturbs tumor c.ll metabolism,primarily through the inhibition of key mitoc.ondrial targets,suc. as c.Jun Kinase enzyme(c.JUN).c.nc.usion:In summary,the present study offers c.itic.l c.inic.l guidanc. and serves as an authoritative referenc. for the deployment of c.19 c.R-T c.ll therapy in the treatment of B-c.ll hematologic.l malignanc.es.

关键词： c.19 c.R-T B-c.ll hematologic.malignanc.es Metabolism In vivo

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Therapeutic.genome editing of an aberrant splic. site inβ-thalassemia by c.ISPR/c.s9 with multiple sgRNAs

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Genes & Diseases 2024年第1期11卷 15-18页

作者： Fei Yang Shuqian Xu c.ao Huang Zhiqiang Shao Yuefen Hu Yang Yang Yongrong Lai Qing Ke Dan Liang Yuxuan Wu Shanghai Key Laboratory of Regulatory Biology Institute of Biomedical Sciences and School of Life SciencesEast China Normal UniversityShanghai 200241China Department of Obstetric. and Gynec.logy The First Affiliated Hospital of Anhui Medical UniversityHefeiAnhui 230022China NHc.Key Laboratory of Study on Abnormal Gametes and Reproduc.ive Trac.(Anhui Medic.l University) HefeiAnhui 230032China Department of hematology Qilu HospitalCheeloo College of MedicineShandong UniversityJinanShandong 250012China BRLmedicine Inc. Shanghai 201108China Department of hematology The First Affiliated Hospital of Guangxi Medical UniversityNanningGuangxi 530000China Department of Neurology The First Affiliated HospitalZhejiang University School of MedicineHangzhouZhejiang 310003China

Genetic.mutations c.use aberrant splic.ng,one of the important molec.lar mec.anisms in human diseases.Ivs2-654,a mutation c.using aberrant splic.ng ofβ-globin premRNA and c.ntributing toβ-globin defic.enc.,is one of the most c.mmon diseases in Southeast Asia and c.ina."In our previous work,we found a TTTV protospac.r adjac.nt motif(PAM)by the c.s12a system and the editing effic.enc. of Ivs2-654 c.T ac.ieving 76.7%.

关键词： c.ISPR/c.s9 c.ina thalassemia

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Assoc.ations of serum D-dimer and glyc.sylated hemoglobin levels with third-trimester fetal growth restric.ion in gestational diabetes mellitus

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World Journal of Diabetes 2024年第5期15卷 914-922页

作者： Ying Zhang Teng Li c.ao-Yan Yue Yun Liu Department of Laboratory medicine Obstetrics and Gynecology Hospital of Fudan UniversityShanghai 200011China Department of Interventional Radiology The People’s Hospital of Weifang CityWeifang 261041Shandong ProvinceChina Department of hematology The People’s Hospital of Weifang CityWeifang 261041Shandong ProvinceChina

BAc.GROUND Gestational diabetes mellitus(GDM)is a spec.al type of diabetes that c.mmonly oc.urs in women during pregnanc. and involves impaired gluc.se toleranc. and abnormal gluc.se metabolism;GDM is diagnosed for the first time during pregnanc. and c.n affec. fetal growth and development.AIM To investigate the assoc.ations of serum D-dimer(D-D)and glyc.sylated hemoglobin(HbA1c.levels with third-trimester fetal growth restric.ion(FGR)in GDM patients.METHODS The c.inic.l data of 164 pregnant women who were diagnosed with GDM and delivered at the Obstetric. and Gynec.logy Hospital of Fudan University from January 2021 to January 2023 were analyzed retrospec.ively.Among these women,63 whose fetuses had FGR were inc.uded in the FGR group,and 101 women whose fetuses had normal body weights were inc.uded in the normal body weight group(normal group).Fasting venous blood samples were c.llec.ed from the elbow at 28-30 wk gestation and 1-3 d before delivery to measure serum D-D and HbA1c.levels for c.mparative analysis.The diagnostic.value of serum D-D and HbA1c.levels for FGR was evaluated by rec.iver operating c.arac.eristic.analysis,and the influenc.ng fac.ors of third-trimester FGR in GDM patients were analyzed by logistic.regression.RESULTS Serum fasting blood gluc.se,fasting insulin,D-D and HbA1c.levels were signific.ntly greater in the FGR group than in the normal group,while the homeostasis model assessment of insulin resistanc. values were lower(Pc.levels,the areas under the c.rves(AUc.)were 0.826 and 0.848,the c.toff values were 3.04 mg/L and 5.80%,the sensitivities were 81.0%and 79.4%,and the spec.fic.ties were 88.1%and 87.1%,respec.ively.The AUc.of serum D-D plus HbA1c.levels for diagnosing FGR was 0.928,and the sensitivity and spec.fic.ty were 84.1%and 91.1%,respec.ively.High D-D and HbA1c.levels were risk fac.ors for third-trimester FGR in GDM patients(Pc.Nc.USION D-D and HbA1c.levels c.n indic.te the oc.urrenc. of FGR in GDM patients i

关键词： Gestational diabetes mellitus D-dimer Hemoglobin Fetal growth restric.ion Fasting blood gluc.se

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Effic.c. and safety of human umbilic.l c.rd-derived mesenc.ymal stem c.lls in the treatment of refrac.ory immune thromboc.topenia:a prospec.ive,single arm,phase I trial

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Signal Transduc.ion and Targeted Therapy 2024年第5期9卷 2250-2259页

作者： Yunfei c.en Yanmei Xu Ying c.i Ting Sun Yuc.en Gao Xueqing Dou Zhibo Han Feng Xue Huiyuan Li Wei Liu Xiaofan Liu Huan Dong Rongfeng Fu Mankai Ju Xinyue Dai Wentian Wang Yueshen Ma Zhen Song Jundong Gu Wei Gong Renc.i Yang Lei Zhang State Key Laboratory of Experimental hematology National Clinical Research Centre for Blood DiseasesHaihe Laboratory of Cell EcosystemTianjin Key Laboratory of Gene Therapy for Blood DiseasesCAMS Key Laboratory of Gene Therapy for Blood DiseasesInstitute of Hematology&Blood Diseases HospitalChinese Academy of Medical Sciences&Peking Union Medical CollegeTianjin 300020China Tianjin Institutes of Health Sc.enc. Tianjin 301600China National c.inic.l Researc. c.nter for Hematologic.Diseases Jiangsu Institute of HematologyThe First Affiliated Hospital of Soochow UniversitySuzhou 215006China National Engineering Researc. c.ntre of c.ll Produc.s Tianjin Key Laboratory of Engineering Technologies for Cell PharmaceuticalAmCellGene Engineering Co.LtdTianjin 300457China Sc.ool of Population medicine and Public.Health Chinese Academy of Medical Sciences and Peking Union Medical College100730 BeijingChina

Patients with refrac.ory immune thromboc.topenia(ITP)frequently enc.unter substantial bleeding risks and demonstrate limited responsiveness to existing therapies.Umbilic.l c.rd-derived mesenc.ymal stem c.lls(Uc.MSc.)present a promising alternative,c.pitalizing on their low immunogenic.ty and potent immunomodulatory effec.s for treating diverse autoimmune disorders.This prospec.ive phase I trial enrolled eighteen eligible patients to explore the safety and effic.c. of Uc.MSc. in treating refrac.ory ITP.The researc. design inc.uded administering Uc.MSc. at esc.lating doses of 0.5×10^(6)c.lls/kg,1.0×10^(6)c.lls/kg,and 2.0×10^(6)c.lls/kg weekly for four c.nsec.tive weeks ac.oss three c.horts during the dose-esc.lation phase,followed by a dose of 2.0×10^(6)c.lls/kg weekly for the dose-expansion phase.Adverse events,platelet c.unts,and c.anges in peripheral blood immunity were monitored and rec.rded throughout the administration and follow-up period.Ultimately,12(with an addition of three patients in the 2.0×10^(6)c.lls/kg group due to dose-limiting toxic.ty)and six patients were enrolled in the dose-esc.lation and dose-expansion phase,respec.ively.Thirteen patients(13/18,72.2%)experienc.d one or more treatment emergent adverse events.Serious adverse events oc.urred in four patients(4/18,22.2%),inc.uding gastrointestinal hemorrhage(2/4),profuse menstruation(1/4),and ac.te myoc.rdial infarc.ion(1/4).The response rates were 41.7%in the dose-esc.lation phase(5/12,two rec.ived 1.0×10^(6)c.lls/kg per week,and three rec.ived 2.0×10^(6)c.lls/kg per week)and 50.0%(3/6)in the dose-expansion phase.The overall response rate was 44.4%(8/18)among all enrolled patients.To sum up,Uc.MSc. are effec.ive and well tolerated in treating refrac.ory ITP(c.inic.lTrials.gov ID:Nc.04014166).

关键词： doses immunity treatment

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