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Dendritic cell-mimicking scaffolds for ex vivo T cell expansion

Bioactive Materials 2023年第3期21卷 241-252页

作者： Hye Sung Kim Tzu-Chieh Ho Moshe J.Willner Michael W.Becker Hae-Won Kim Kam W.Leong Department of Biomedical Engineering Columbia UniversityNew YorkNYUSA institute of Tissue Regeneration Engineering Dankook UniversityCheonanRepublic of Korea wilmot cancer institute University of Rochester Medical CenterRochesterNYUSA Department of Regenerative Dental Medicine College of DentistryDankook UniversityCheonanRepublic of Korea Department of Nanobiomedical Science and BK21 PLUS NBM Global Research Center for Regenerative Medicine Dankook UniversityCheonanRepublic of Korea Mechanobiology Dental Medicine Research Center Dankook UniversityCheonanRepublic of Korea Department of Systems Biology Columbia University Irving Medical CenterNew YorkNY10032USA

We propose an ex vivo T cell expansion system that mimics natural antigen-presenting cells(APCs)for adoptive cell therapy(ACT).Microfiber scaffolds coated with dendritic cell(DC)membrane replicate physicochemical properties of dendritic cells specific for T cell activation such as rapid recognition by T cells,long duration of T cell tethering,and DC-specific co-stimulatory *** DC membrane-coated scaffold is first surface-immobilized with T cell stimulatory ligands,anti-CD3(αCD3)and anti-CD28(αCD28)antibodies,followed by adsorption of releasable interleukin-2(IL-2).The scaffolds present both surface and soluble cues to T cells ex vivo in the same way that these cues are presented by natural APCs in *** demonstrate that the DC-mimicking scaffold promotes greater polyclonal expansion of primary human T cells as compared toαCD3/αCD28-func-tionalized *** importantly,major histocompatibility complex molecules derived from the DC membrane of the scaffold allow antigen-specific T cell expansion with target cell-specific killing *** addition,most of the expanded T cells(~97%)can be harvested from the scaffold by density gradient ***,the DC-mimicking scaffold offers a scalable,modular,and customizable platform for rapid expansion of highly functional T cells for ACT.

关键词： Adoptive cell therapy Ex vivo T cell expansion Cytotoxic T cell Dendritic cell membrane Cell membrane coating Scaffold

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Corrigendum to‘New therapy targeting differential androgen receptor signaling in prostate cancer stem/progenitor ***-stem/progenitor cells’

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Journal of Molecular Cell Biology 2020年第12期12卷 991-992页

作者： Soo Ok Lee Zhifang Ma Chiuan-Ren Yeh Jie Luo Tzu-Hua Lin Kuo-Pao Lai Shinichi Yam ashita Liang Liang Jing Tian Lei Li Qi Jiang Chiung-Kuei Huang Yuanjie Niu Shuyuan Yeh and Chawnshang Chang George Whipple Lab for cancer Research Department of PathologyUniversity of Rochester Medical CenterRochesterNY 14642USA George Whipple Lab for cancer Research Department of UrologyUniversity of Rochester Medical CenterRochesterNY 14642USA George W hipple Lab for cancer Research Department of Radiation OncologyUniversity of Rochester Medical CenterRochesterNY 14642USA George Whipple Lab for cancer Research The Wilmot Cancer CenterUniversity of Rochester Medical CenterRochesterNY 14642USA Department of Urology First Hospital of Shanxi Medical UniversityTaiyuan 030001China Sex Hormone Research Center Department of UrologyThe First Affiliated HospitalXi an Jiaotong UniversityXi an 710061China Chawnshang Chang Sex Hormone Research Center Tianjin Institute of UrologyTianjin Medical UniversityTianjin 300211China Sex Hormone Research Center China Medical University and HospitalTaichung A04

In this article,there were errors in the images presented in Figure 3Ab(bottom left)and Figure 5D(2nd and 4th columns).These were caused by miss-insertion of the images during preparation of the manuscript for *** raw data of the images in Figure 5D were lost,the authors re-performed the whole experiment and provided new similar results(both images and quantitation graphs)for an *** corrected Figure 3Ab left panel and updated Figure 5D are shown as *** details have been corrected only in this corrigendum to preserve the published version of *** authors assure that the original results or conclusions are not altered and they apologize for the mistake.

关键词： Figure corrected details

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The roles of bone remodeling in normal hematopoiesis and age-related hematological malignancies

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Bone Research 2023年第2期11卷 273-291页

作者： Hengwei Zhang Jane LLiesveld Laura MCalvi Brea CLipe Lianping Xing Michael WBecker Edward MSchwarz Shu-Chi A.Yeh Center for Musculoskeletal Research University of Rochester Medical Center601 Elmwood AveBox 665RochesterNY14642USA Department of Pathology and Laboratory Medicine University of Rochester Medical CenterRochesterNYUSA wilmot cancer Center University of Rochester Medical CenterRochesterNYUSA Department of Medicine Division of Hematology/Oncology and Bone Marrow Transplantation ProgramUniversity of Rochester Medical CenterRochesterNYUSA Department of Medicine Division of Endocrinology/MetabolismUniversity of Rochester Medical CenterRochesterNYUSA Department of Orthopaedics University of Rochester Medical CenterRochesterNYUSA Department of Medicine Division of Allergy/Immunology/RheumatologyUniversity of Rochester Medical CenterRochesterNYUSA Department of Biomedical Engineering University of RochesterNYUSA Department of Physiology/Pharmacology University of Rochester Medical CenterRochesterNYUSA

Prior research establishing that bone interacts in coordination with the bone marrow microenvironment(BMME)to regulate hematopoietic homeostasis was largely based on analyses of individual bone-associated cell *** advances in intravital imaging has suggested that the expansion of hematopoietic stem cells(HSCs)and acute myeloid leukemia cells is restricted to bone marrow microdomains during a distinct stage of bone *** findings indicate that dynamic bone remodeling likely imposes additional heterogeneity within the BMME to yield differential clonal responses.A holistic understanding of the role of bone remodeling in regulating the stem cell niche and how these interactions are altered in age-related hematological malignancies will be critical to the development of novel *** advance this understanding,herein,we provide a synopsis of the cellular and molecular constituents that participate in bone turnover and their known connections to the hematopoietic ***,we elaborate on the coupling between bone remodeling and the BMME in homeostasis and age-related hematological malignancies and after treatment with bone-targeting *** then discuss unresolved questions and ambiguities that remain in the field.

关键词： remodeling homeostasis likely

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Polatuzumab Vedotin in Previously Untreated Diffuse Large B-Cell Lymphoma

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四川生理科学杂志 2021年第10期43卷 1699-1699页

作者： HervéTilly From the Department of Hematology and INSERM Unité 1245 Centre Henri-Becquerel and University of Rouen Rouen (H.T.) Université de Lille Centre Hospitalier Universitaire (CHU) Lille ULR 7365 - GRITA - Groupe de Recherche sur les Formes Injectables et les Technologies Associées Lille (F.M.) CHU de Montpellier Montpellier (C.H.) the Department of Hematology Institut Universitaire du Cancer Toulouse-Oncopole Toulouse (L.O.) and the Department of Hematology Centre Hospitalier Régional Universitaire - Besançon Besançon (A.C.) - all in France the Centre for Lymphoid cancer at BC cancer and the University of British Columbia Vancouver (L.H.S.) the Odette Cancer Centre Sunnybrook Health Sciences Centre University of Toronto Toronto (M.C.C.) and F. Hoffmann-La Roche Mississauga ON (M.Y.) - all in Canada the wilmot cancer institute University of Rochester Rochester (J.W.F.) and Memorial Sloan Kettering Cancer Center New York (M.M. G.S.) - both in New York the First Faculty of Medicine Charles University and the General University Hospital Prague Czech Republic (M.T.) the Willamette Valley cancer institute and Research Center the US Oncology Network Eugene OR (J.P.S.) Rocky Mountain cancer Centers Aurora CO (J.M.B.) Memorial Sloan Kettering cancer Center Montvale NJ (M.M.) the Department of Hematology and Rheumatology Kindai University Faculty of Medicine Osaka-Sayama City (S.R.) and the National Cancer Center Hospital Tokyo (K.I.) - both in Japan Washington University in St. Louis St. Louis (N.M.-S.) the Maria Sklodowska-Curie National Research institute of Oncology Krakow Poland (W.J.) Peking University cancer Hospital Beijing (Y.S.) the 3rd Medical Department Paracelsus Medical University Salzburg Cancer Research Institute-Center for Clinical Cancer and Immunology Trials and Cancer Cluster Salzburg Salzburg Austria (R.G.) the Feofaniya Clinical Hospital Kyiv Ukraine (L.M.) Hospital San Pedro de Alcántara Cáceres (J.M.B.-B.) and the Department of Hematology Vall d'He

Background:Diffuse large B-cell lymphoma(DLBCL)is typically treated with rituximab,cyclophosphamide,doxorubicin,vincristine,and prednisone(R-CHOP).However,only 60%of patients are cured with *** vedotin is an antibody-drug conjugate targeting CD79b,which is ubiquitously expressed on the surface of malignant B ***:We conducted a double-blind,placebo-controlled,international phase 3 trial to evaluate a modified regimen of RCHOP(pola-R-CHP),in which vincristine was replaced with polatuzumab vedotin,as compared with standard R-CHOP,in patients with previously untreated intermediate-risk or high-risk *** 18 to 80 years of age were randomly assigned in a 1:1 ratio to receive six cycles of either pola-R-CHP or R-CHOP,plus two cycles of rituximab *** primary end point was investigator-assessed progression-free *** end points included overall survival and safety.

关键词： CHOP assessed alone

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Age at diagnosis of type 2 diabetes and cardiovascular risk factor profile:A pooled analysis

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World Journal of Diabetes 2022年第3期13卷 260-271页

作者： Mary M Barker Francesco Zaccardi Emer M Brady Gaurav S Gulsin Andrew P Hall Joseph Henson Zin ZinHtike Kamlesh Khunti Gerald P McCann Emma L Redman David R Webb Emma G wilmot Tom Yates Jian Yeo Melanie J Davies Jack A Sargeant Diabetes Research Centre University of LeicesterLeicester General HospitalLeicester LE54PWUnited Kingdom Department of Cardiovascular Sciences Glenfield HospitalUniversity of LeicesterLeicester LE39QPUnited Kingdom The Hanning Sleep Laboratory University Hospitals of Leicester NHS TrustUniversity of LeicesterLeicester LE54PWUnited Kingdom National institute for Health Research Leicester Biomedical Research CentreLeicester LE54PWUnited Kingdom Leicester Diabetes Centre University Hospitals of Leicester NHS TrustLeicester LE54PWUnited Kingdom National institute for Health Research Applied Research Collaboration East MidlandsLeicester LE54PWUnited Kingdom Department of Diabetes University Hospitals of Derby and Burton NHS Foundation TrustDerby DE223NEUnited Kingdom

BACKGROUND The diagnosis of type 2 diabetes(T2D)in younger adults,an increasingly common public health issue,is associated with a higher risk of cardiovascular complications and mortality,which may be due to a more adverse cardiovascular risk profile in individuals diagnosed at a younger *** To investigate the association between age at diagnosis and the cardiovascular risk profile in adults with *** A pooled dataset was used,comprised of data from five previous studies of adults with T2D,including 1409 participants of whom 196 were diagnosed with T2D under the age of 40 *** and blood biomarker measurements included body weight,body mass index(BMI),waist circumference,body fat percentage,glycaemic control(HbA1c),lipid profile and blood *** and multivariable linear regression models,adjusted for diabetes duration,sex,ethnicity and smoking status,were used to investigate the association between age at diagnosis and each cardiovascular risk *** A higher proportion of participants diagnosed with T2D under the age of 40 were female,current smokers and treated with glucose-lowering medications,compared to participants diagnosed later in *** diagnosed with T2D under the age of 40 also had higher body weight,BMI,waist circumference and body fat percentage,in addition to a more adverse lipid profile,compared to participants diagnosed at an older *** results showed that each one year reduction in age at diagnosis was significantly associated with 0.67 kg higher body weight[95%confidence interval(CI):0.52-0.82 kg],0.18 kg/m^(2) higher BMI(95%CI:0.10-0.25)and 0.32 cm higher waist circumference(95%CI:0.14-0.49),after adjustment for duration of diabetes and other *** age at diagnosis was also significantly associated with higher HbA1c,total cholesterol,low-density lipoprotein cholesterol and *** The diagnosis of T2D earlier in life is associated with a worse cardi

关键词： Type 2 diabetes mellitus Early-onset adult type 2 diabetes Age of onset Cardiovascular risk Young adults Glycaemic control Obesity

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