Advances in cell and gene therapy最新文献_第8页

Corrigendum: Dawn of chimeric antigen receptor T cell therapy in non-Hodgkin Lymphoma 勘误:嵌合抗原受体T细胞治疗非霍奇金淋巴瘤的曙光

Advances in cell and gene therapy Pub Date : 2019-01-13 DOI: 10.1002/acg2.44

Karlo Perica, M. Lia Palomba, Renier J. Brentjens

引用次数: 0

High-dose chemotherapy and autologous transplantation for testicular germ cell tumors 睾丸生殖细胞肿瘤的高剂量化疗和自体移植

Advances in cell and gene therapy Pub Date : 2019-01-12 DOI: 10.1002/acg2.47

Naimisha Marneni, Navneet S. Majhail, Timothy D. Gilligan, Moshe C. Ornstein

{"title":"High-dose chemotherapy and autologous transplantation for testicular germ cell tumors","authors":"Naimisha Marneni, Navneet S. Majhail, Timothy D. Gilligan, Moshe C. Ornstein","doi":"10.1002/acg2.47","DOIUrl":"10.1002/acg2.47","url":null,"abstract":"Testicular cancer is the most common solid organ malignancy affecting males between 15 and 35 years of age with an annual incidence of approximately 9300 in the United States.1 Germ cell tumors (GCTs) are the most common type of testicular cancer and are broadly categorized as seminomatous (SGCTs) and nonseminomatous germ cell tumors (NSGCTs). Therapeutic advances and utmost sensitivity to cisplatinbased combination chemotherapy make it one of the most curable solid neoplasms, even in the presence of metastatic disease with a 5year survival rate of approximately 95%.1 The standard chemotherapy regimen of bleomycin, etoposide, and cisplatin (BEP) cures a significant proportion of patients. However, despite these advances, a subset of patients have refractory disease or develop disease recurrence requiring salvage chemotherapy. Salvage chemotherapy options include conventionaldose chemotherapy (CDCT) with cisplatin and ifosfamide plus paclitaxel (TIP) or vinblastine (VeIP) or etoposide (VIP), or highdose chemotherapy with autologous hematopoietic stem cell transplantation (HDCT/HSCT).2-4 HDCT with HSCT has been available as a therapeutic option since 1986 and has provided cure to selected patients even as a third line regimen.5 We provide data for and our approach to the utilization of HDCT with HSCT in advanced GCTs.","PeriodicalId":72084,"journal":{"name":"Advances in cell and gene therapy","volume":"2 2","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-01-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/acg2.47","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42083015","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 2

Allogeneic CD27-depleted cells in adoptive cell therapy 过继细胞治疗中的异基因CD27耗竭细胞

Advances in cell and gene therapy Pub Date : 2019-01-09 DOI: 10.1002/acg2.45

Aimee C. Talleur, Jean-Yves Métais, Ying Li, Robert E. Throm, Heather Tillman, Barbara Rooney, Ardiana Moustaki, Wing Leung

{"title":"Allogeneic CD27-depleted cells in adoptive cell therapy","authors":"Aimee C. Talleur, Jean-Yves Métais, Ying Li, Robert E. Throm, Heather Tillman, Barbara Rooney, Ardiana Moustaki, Wing Leung","doi":"10.1002/acg2.45","DOIUrl":"10.1002/acg2.45","url":null,"abstract":"Adoptive cell therapy (ACT) has emerged as an effective treatment for some cancers. However, allogeneic cell applications are in part limited by the risk of alloreactive T-cell subsets causing graft-versus-host-disease (GVHD). We therefore hypothesized that the use of CD27-depleted cells (containing natural killer [NK] cells and effector memory T-cells; without naïve or central memory T-cells) would offer protection from pathogens and GVHD, while also providing anticancer activity when genetically engineered with a chimeric antigen receptor (CAR). In this work, cell phenotypes were evaluated using flow cytometry. In vitro immunologic memory and alloreactivity were tested using lymphocyte proliferation assays. In vivo GVHD potential was assessed using NOD scid gamma (NSG) mice. Anticancer activity of CAR-transduced CD27-depleted cells was tested in vitro via a cytotoxicity assay and in vivo using NSG mice. Our results confirmed that the CD27-depleted cell fraction was enriched for NK cells, effector memory CD4pos T cells and terminal effector memory CD8pos T cells. CD27-depleted cells had strong immunologic response against common pathogens in vitro, and less GVHD potential in vitro and in vivo. CD27-depleted cells could be transduced with a CAR vector produced by stable cell lines, and demonstrated significant antileukemic activity in vitro and in vivo. These findings suggest that CD27-depletion is a promising approach to using allogeneic cells in ACT, potentially providing infection and cancer control simultaneously but having low risk of causing GVHD.","PeriodicalId":72084,"journal":{"name":"Advances in cell and gene therapy","volume":"2 2","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/acg2.45","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45419654","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 1

Viral infections after allogeneic hematopoietic stem cell transplant 异体造血干细胞移植后的病毒感染

Advances in cell and gene therapy Pub Date : 2018-12-28 DOI: 10.1002/acg2.43

Alankrita Taneja, Joseph H. Chewning, Ayman Saad

引用次数: 3

Biomarker profiling of steroid-resistant chronic GvHD patients undergoing extracorporeal photopheresis demonstrates high ST2 levels at treatment onset and decline during therapy 接受体外光疗的类固醇抵抗性慢性GvHD患者的生物标志物分析显示，治疗开始时ST2水平较高，治疗期间下降

Advances in cell and gene therapy Pub Date : 2018-12-19 DOI: 10.1002/acg2.32

Neil Dunavin, Mitchell W. Braun, Meizhang Li, Andrew K. Godwin, Sunil Abhyankar, Thomas M. Yankee

{"title":"Biomarker profiling of steroid-resistant chronic GvHD patients undergoing extracorporeal photopheresis demonstrates high ST2 levels at treatment onset and decline during therapy","authors":"Neil Dunavin, Mitchell W. Braun, Meizhang Li, Andrew K. Godwin, Sunil Abhyankar, Thomas M. Yankee","doi":"10.1002/acg2.32","DOIUrl":"10.1002/acg2.32","url":null,"abstract":"Chronic graft-versus host disease (GvHD) affects approximately 30%-70% of patients undergoing hematopoietic stem cell transplantation. Extracorporeal photopheresis (ECP) is an immunomodulatory therapy that is often used as a second-line therapeutic option for steroid-resistant chronic GvHD. There is a several week delay between the onset of ECP and clinical improvement in symptoms. Thus, a biomarker that precedes improvement in disease activity or predicts response to therapy would be of clinical value. In this study, we sought to determine how previously studied GvHD biomarkers change over a course of ECP therapy. Seven chronic GvHD biomarkers (ST2, MMP-3, CXCL9, CXCL10, CXCL11, BAFF, and CD163) were measured by ELISA in 16 patients before and after 2 months of ECP. Initial ST2 levels were high compared to healthy donors and patient samples required more than the manufacturer-recommended dilution. The median ST2 level decreased over the first 2 months of treatment (193 v. 96 ng/mL, P = 0.03); the other biomarkers did not change significantly. Serial ST2 levels at 2, 4, and 6 months after ECP initiation showed that ST2 levels declined over the course of therapy. The results of this study show that ST2 is substantially elevated and declines during therapy in patients who receive ECP as a second-line therapy for chronic GvHD.","PeriodicalId":72084,"journal":{"name":"Advances in cell and gene therapy","volume":"2 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2018-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/acg2.32","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42712717","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 3

Advances in ex vivo T cell depletion – where do we stand? 离体T细胞耗竭的进展——我们的立场如何？

Advances in cell and gene therapy Pub Date : 2018-12-04 DOI: 10.1002/acg2.29

Adam R. Bryant, Miguel-Angel Perales

{"title":"Advances in ex vivo T cell depletion – where do we stand?","authors":"Adam R. Bryant, Miguel-Angel Perales","doi":"10.1002/acg2.29","DOIUrl":"https://doi.org/10.1002/acg2.29","url":null,"abstract":"Graft-versus-host (GVHD) is an important cause of morbidity and mortality after allogeneic hematopoietic cell transplantation (HCT). As donor T cells are recognized as key drivers of GVHD, some approaches to prevent GVHD have focused on T cell depletion of the allograft. In this review we summarize methods and outcomes of ex vivo T cell depleted (TCD) HCT with a focus on CD34+ selection. This platform is efficacious in preventing acute and chronic GVHD across a wide range of hematologic malignancies, and with the exception of chronic myeloid leukemia, is not associated with adverse relapse or survival outcomes compared to conventional GVHD prophylaxis platforms. In retrospective comparisons recipients of CD34+ selected HCT have higher rates of GVHD-free relapse-free survival (GRFS) than conventional HCT counterparts. Although CD34+ selected allografts require myeloablative and antithymocyte-globulin based conditioning to support engraftment, abrogation of calcineurin inhibitors and methotrexate in this approach reduces its toxicity such that it can be considered in select older and more comorbid patients who could benefit from ablative HCT. A trial comparing GVHD prophylaxis regimens (BMT CTN 1301, NCT 02345850) has completed accrual and will be the first to compare CD34+ selected HCT with conventional HCT in a randomized prospective setting. Its findings have a potential to establish CD34+ selected HCT as a new standard-of-care platform for GVHD prevention.","PeriodicalId":72084,"journal":{"name":"Advances in cell and gene therapy","volume":"2 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2018-12-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/acg2.29","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71942407","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 3

Donor selection for haploidentical hematopoietic cell transplantation- practice guidance 单倍体造血细胞移植的供体选择-实践指南

Advances in cell and gene therapy Pub Date : 2018-12-03 DOI: 10.1002/acg2.42

Yu-Qian Sun, Ying-Jun Chang, Xiao-Jun Huang

{"title":"Donor selection for haploidentical hematopoietic cell transplantation- practice guidance","authors":"Yu-Qian Sun, Ying-Jun Chang, Xiao-Jun Huang","doi":"10.1002/acg2.42","DOIUrl":"10.1002/acg2.42","url":null,"abstract":"Haploidentical hematopoietic cell transplantation (haplo-HCT) using either T-cell depletion or T-cell repletion (Beijing protocol or post-transplantation cyclophosphamide) has shown great advancements in recent years. Haplo-HCT can achieve comparable outcomes for transplantation from matched sibling donors and unrelated donors and has been used increasingly worldwide. For almost every patient, multiple haploidentical donors are available. Therefore, it is necessary to choose the best donor. However, there is no universal consensus on donor selection. The aim of this review was to discuss the general principles of and controversial factors related to donor selection. Several principles have been widely accepted. For example, human leukocyte antigen disparity is no longer taken into account, donor-specific antibodies should be avoided, and younger donors and ABO matches are preferred. However, factors such as donor gender, family relationship, cytomegalovirus serological status, and natural killer cell alloreactivity are still controversial. Moreover, the factors may depend on the transplantation regimen. Finally, we summarize practical points for donor selection according to different haplo-HCT protocols.","PeriodicalId":72084,"journal":{"name":"Advances in cell and gene therapy","volume":"2 2","pages":""},"PeriodicalIF":0.0,"publicationDate":"2018-12-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/acg2.42","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"48991078","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Do hypomethylating agents prevent relapse after Allo-HCT? 低甲基化药物能防止Allo-HCT后复发吗？

Advances in cell and gene therapy Pub Date : 2018-11-29 DOI: 10.1002/acg2.30

Thomas Schroeder, Christina Rautenberg, Rainer Haas, Ulrich Germing, Guido Kobbe

{"title":"Do hypomethylating agents prevent relapse after Allo-HCT?","authors":"Thomas Schroeder, Christina Rautenberg, Rainer Haas, Ulrich Germing, Guido Kobbe","doi":"10.1002/acg2.30","DOIUrl":"10.1002/acg2.30","url":null,"abstract":"Relapse is the main cause of treatment failure in patients with acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS) and limits the curative potential of allogeneic blood stem cell transplantation (allo-HCT). Many patients can either not tolerate or do not achieve durable remissions through commonly used treatment options such as salvage chemotherapy, donor lymphocyte infusions (DLI), and/or second transplants. Thus, patients who relapse after allo-HCT have a very poor prognosis with the currently available therapies implicating the great medical need for relapse prevention. After having demonstrated efficacy and tolerability as salvage therapy in patients with myeloid malignancies who relapse after allo-HCT the hypomethylating agents azacitidine (Aza) and decitabine (DAC) have also been tested as prophylactic and preemptive approaches in patients with AML and MDS after allo-SCT. Here, we summarize the current literature reporting on results from prospective trials and retrospective analyses regarding the prophylactic and preemptive use of Aza and DAC after allo-SCT and aim to give an answer if these hypomethylating agents (HMA) are able to prevent relapse of myeloid malignancies after allo-HCT.","PeriodicalId":72084,"journal":{"name":"Advances in cell and gene therapy","volume":"2 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2018-11-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/acg2.30","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"47908124","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 1

From bench to bedside: Exploiting memory NK cell responses to leukemia 从工作台到床边：利用记忆性NK细胞对白血病的反应

Advances in cell and gene therapy Pub Date : 2018-11-23 DOI: 10.1002/acg2.28

Marina Schmidt, Maya C. André

{"title":"From bench to bedside: Exploiting memory NK cell responses to leukemia","authors":"Marina Schmidt, Maya C. André","doi":"10.1002/acg2.28","DOIUrl":"10.1002/acg2.28","url":null,"abstract":"Natural killer (NK) cells belong to innate lymphoid immune cells that contribute to antitumor responses without requiring prior sensitization. There is strong evidence that NK cells may induce graft-vs-leukemia (GvL) effect without causing graft-vs-host disease (GvHD), and significant efforts are currently undertaken to design and optimize NK cell-based immunotherapeutic strategies against human cancers, particularly against leukemias. However, the results of a number of adoptive NK cell transfer studies have been somewhat disappointing. This may be explained with difficulties in integrating the sequentially appearing activating signals into a directed NK cell response and may also be due to the lack of longevity of the transferred NK cells. The recent understanding that NK cells share developmental and homeostatic properties with T cells led to the hypothesis that NK cells should be able to elicit an (antigen-specific) recall response and should as such theoretically confer the potential for self-renewal and clonal expansion which may translate into longevity. Although immunological memory is per se a hallmark of the adaptive immune system, recent studies performed in mice and humans indicate that NK cells may indeed acquire (under certain conditions) features of adaptive immune cells. This review pursues the aim of providing a general understanding of the cellular and molecular aspects of various forms of memory NK cells with inherent antitumor properties and attempt to describe the translation of this knowledge into recent clinical adoptive transfer protocols with the aim of optimally harnessing the memory NK cell response to certain leukemias.","PeriodicalId":72084,"journal":{"name":"Advances in cell and gene therapy","volume":"2 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2018-11-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/acg2.28","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"47628810","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 2

Meeting report: Advances in minimal residual disease testing in multiple myeloma 2018 会议报告:2018年多发性骨髓瘤微小残留病检测进展

Advances in cell and gene therapy Pub Date : 2018-11-09 DOI: 10.1002/acg2.26

Ola Landgren, Even H. Rustad

{"title":"Meeting report: Advances in minimal residual disease testing in multiple myeloma 2018","authors":"Ola Landgren, Even H. Rustad","doi":"10.1002/acg2.26","DOIUrl":"10.1002/acg2.26","url":null,"abstract":"This report summarizes the 5th annual symposium on minimal residual disease (MRD) testing in multiple myeloma gathered experts from academia, industry and the FDA in New York City on 14 September 2018. Three recommendations were made: (a) MRD testing should be performed in patients who achieve a very good partial response (VGPR) in addition to complete response (CR); (b) MRD negativity at one tumor cell in 1 000 000 bone marrow cells (10−6) should be considered as a response category alongside the current definition of MRD negativity at 10−5; and (c) clinical trials reports should specify the sensitivity of MRD testing as well as the applied threshold for MRD negativity (ie, 10−5 or 10−6), and if possible report outcome data for both MRD thresholds. Overall, as discussed at the meeting, there is already solid evidence that bone marrow based MRD assessment is one of the strongest prognostic factors in multiple myeloma, and deeper responses correlate with increasingly favorable outcomes. Indeed, achieving MRD negativity appears to be more important than what treatment was used to get there. Going forward, there is a need for clinical trials focusing on MRD-directed therapy to determine the role of MRD testing in everyday clinical decision-making. Standardization of MRD testing and harmonization across centers will make it easier to learn from common experiences. Ongoing efforts are anticipated to establish MRD status as a regulatory endpoint for accelerated drug approval in multiple myeloma in the near future.","PeriodicalId":72084,"journal":{"name":"Advances in cell and gene therapy","volume":"2 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2018-11-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/acg2.26","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"44641732","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 18