Advances in cell and gene therapy最新文献_第5页

Selecting patients with primary myelofibrosis for stem cell transplant using clinical, mutational, and transplant-specific profiles 使用临床、突变和移植特异性资料选择原发性骨髓纤维化患者进行干细胞移植

Advances in cell and gene therapy Pub Date : 2020-01-29 DOI: 10.1002/acg2.80

Nico Gagelmann, Nicolaus Kröger

{"title":"Selecting patients with primary myelofibrosis for stem cell transplant using clinical, mutational, and transplant-specific profiles","authors":"Nico Gagelmann, Nicolaus Kröger","doi":"10.1002/acg2.80","DOIUrl":"10.1002/acg2.80","url":null,"abstract":"As with other hematologic malignancies, the management of patients with MF has very much entered the molecular era. The prognostic impact of several driver and nondriver mutations is now well-established; this has obvious relevance to both patient selection for allogeneic hematopoietic cell transplantation and posttransplant outcomes. For transplant, present JAK2 or triple-negative driver mutation genotype together with present ASXL1 mutation may provide best utility for counseling patients with respect to posttransplant outcome, together with clinical (performance status, age, and leukocyte and platelet counts) and transplant-related factors (donor relation). Different conditioning intensities do not seem to play a role with regards to outcome posttransplant but still need to be compared in the molecular era. While ruxolitinib provides clinical benefits for patients before transplant, more studies on the finetuning and integration of ruxolitinib into the transplant algorithm are needed. In conclusion, as clinically important risk stratification has been achieved throughout the disease course and new targeted agents become increasingly available, a collaborative and integrative approach is needed to translate new biological insights to personalized/tailored and timed therapy for patients with myelofibrosis.","PeriodicalId":72084,"journal":{"name":"Advances in cell and gene therapy","volume":"3 2","pages":""},"PeriodicalIF":0.0,"publicationDate":"2020-01-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/acg2.80","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"47434323","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

RNA ImmunoGenic Assay: Simple method for detecting immunogenicity of in vitro transcribed mRNA RNA免疫原性试验:检测体外转录mRNA免疫原性的简单方法

Advances in cell and gene therapy Pub Date : 2020-01-28 DOI: 10.1002/acg2.79

AKM Ashiqul Haque, Petra Weinmann, Sumit Biswas, Rupert Handgretinger, Markus Mezger, Michael S. D. Kormann, Justin S. Antony

{"title":"RNA ImmunoGenic Assay: Simple method for detecting immunogenicity of in vitro transcribed mRNA","authors":"AKM Ashiqul Haque, Petra Weinmann, Sumit Biswas, Rupert Handgretinger, Markus Mezger, Michael S. D. Kormann, Justin S. Antony","doi":"10.1002/acg2.79","DOIUrl":"10.1002/acg2.79","url":null,"abstract":"In vitro transcribed (IVT) mRNA therapies is a promising approach for the effective and safe treatment of various diseases. However, IVT-mRNA triggers immune responses due to recognition by human RNA sensors, but incorporation of chemically modified nucleosides have been shown to reduce such responses. Nonetheless, an assay reflecting the complexity of the human immune system is still needed. Here, we present a simple and fast ex vivo method called “RNA Immunogenic Assay” for measuring the immunogenicity of IVT-mRNA in human whole blood. Chemically modified and unmodified mRNA were complexed with a transfection reagent (TransIT), and co-incubated in human whole blood and specific cytokines were quantified (TNF-α, INF-α, IL-6, and IL-12p70) using ELISAs. The qPCR analysis was conducted to unveil the activation of specific immune pathway. Our findings demonstrated that the complete replacement of uridine with pseudouridine reduced TNF-α, IL-6, and IL-12p70 levels and did not elevate the expression of genes involved in immune response against RNA including IRF7/3, EIF2A, & RNASEL. In addition, we observed that the transcript length was not found to be a confounding factor in RNA immunogenicity generation and our assay provide the feasibility to dissect donor specific immune response against mRNA therapeutics.","PeriodicalId":72084,"journal":{"name":"Advances in cell and gene therapy","volume":"3 2","pages":""},"PeriodicalIF":0.0,"publicationDate":"2020-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/acg2.79","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"48044455","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 2

Update on the classification of myeloid neoplasms: The 2016 revised World Health Organization classification of hematopoietic and lymphoid neoplasms 髓系肿瘤分类的最新进展:2016年修订的世界卫生组织造血和淋巴肿瘤分类

Advances in cell and gene therapy Pub Date : 2019-11-25 DOI: 10.1002/acg2.78

Valentina Sangiorgio, Attilio Orazi

引用次数: 1

Prevention of relapse after allogeneic stem cell transplantation in acute myeloid leukemia: Updates and challenges 预防急性髓系白血病异体干细胞移植后复发:最新进展和挑战

Advances in cell and gene therapy Pub Date : 2019-11-08 DOI: 10.1002/acg2.77

Shinto F. Thekkudan, Marcos de Lima, Leland Metheny

{"title":"Prevention of relapse after allogeneic stem cell transplantation in acute myeloid leukemia: Updates and challenges","authors":"Shinto F. Thekkudan, Marcos de Lima, Leland Metheny","doi":"10.1002/acg2.77","DOIUrl":"10.1002/acg2.77","url":null,"abstract":"Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a potentially curative treatment for acute myeloid leukemia (AML). Reduced intensity regimens, alternative graft sources, advances in HLA-matching, improved supportive care, and tailored graft versus host disease (GVHD) prophylaxis have led to a wider application of allo-HSCT to eligible patients. Unfortunately, 30-40% of patients with AML will relapse after transplant and this is the major cause of treatment failure. Careful consideration should be paid in choosing the type of graft, graft source, and conditioning regimen to minimize the risk of disease recurrence. In addition, maintenance therapy following allo-HSCT is a potential method to keep the disease in remission, especially in those with high-risk disease characteristics. Pharmacological targeted agents with low side effect profile such as tyrosine kinase inhibitors, hypomethylating agents (HMAs), HDAC inhibitors, antibody drug conjugates (ADCs), isocitrate dehydrogenase inhibitors, and hedgehog inhibitors may prevent relapse in posttransplant setting and are under investigation. Immunological therapies including donor lymphocyte infusions (DLIs), natural killer (NK) cell therapy, peptide vaccine targeting tumor antigens, and adoptive T-cell therapies all hold promises in this area as well. As targeted agents and immunotherapies continue to be developed, patients at high risk of recurrence may benefit from prophylactic maintenance therapy. Here we review the current landscape in this rapidly evolving clinical setting.","PeriodicalId":72084,"journal":{"name":"Advances in cell and gene therapy","volume":"3 2","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/acg2.77","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"44932436","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

Important aspects of T-cell collection by apheresis for manufacturing chimeric antigen receptor T cells 利用单采收集T细胞制造嵌合抗原受体T细胞的重要方面

Advances in cell and gene therapy Pub Date : 2019-10-02 DOI: 10.1002/acg2.75

Monika Paroder, Nguyet Le, Huy P. Pham, Suzanne R. Thibodeaux

{"title":"Important aspects of T-cell collection by apheresis for manufacturing chimeric antigen receptor T cells","authors":"Monika Paroder, Nguyet Le, Huy P. Pham, Suzanne R. Thibodeaux","doi":"10.1002/acg2.75","DOIUrl":"10.1002/acg2.75","url":null,"abstract":"Chimeric antigen receptor (CAR)-T cells have proven to be an effective cancer therapy for CD19-expressing neoplasms. Efforts to optimize the manufacturing process can help to ensure the efficacy and safety of the therapy. Peripheral blood T cells, which serve as the source material, are collected by apheresis. However, the majority of apheresis collection protocols do not selectively collect T cells, but rather isolate the mononuclear cell (MNC) layer, which also contains other mononuclear leukocytes present in the peripheral blood. Since currently CAR-T cells are autologous, the patient's clinical condition is a major factor in the planning, coordination, and execution of the apheresis procedure to subsequently manufacture the product successfully. Efforts have been made to identify predictors of a successful collection (ie, precollection peripheral blood CD3+ count). The characteristics of the source material influences the manufacturing process directly, and therefore affects the quantity, viability, immune cell composition, and T cell phenotypic makeup of the final product. Here we review the CAR-T cell manufacturing process from the apheresis perspective, highlighting considerations before, during, and after collection that could potentially alter the outcome of the manufacturing process and ultimately, the safety and efficacy of the therapy for the patient.","PeriodicalId":72084,"journal":{"name":"Advances in cell and gene therapy","volume":"3 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/acg2.75","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43003330","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: 5

Recently approved molecularly targeted therapies in AML 最近批准的AML分子靶向治疗

Advances in cell and gene therapy Pub Date : 2019-10-01 DOI: 10.1002/acg2.76

Nikolaos Papadantonakis, Harry P. Erba

引用次数: 0

Advances in relapsed/refractory follicular lymphoma therapeutics 复发/难治性滤泡性淋巴瘤的治疗进展

Advances in cell and gene therapy Pub Date : 2019-09-21 DOI: 10.1002/acg2.74

Evgeniya V. Kharchenko, John W. Sweetenham

{"title":"Advances in relapsed/refractory follicular lymphoma therapeutics","authors":"Evgeniya V. Kharchenko, John W. Sweetenham","doi":"10.1002/acg2.74","DOIUrl":"10.1002/acg2.74","url":null,"abstract":"Of 75 000 new cases of Non-Hodgkin lymphoma (NHL) expected in 2018 in USA, World Health Organization (WHO) data suggest that follicular lymphoma (FL) and diffuse large B-cell lymphoma (DLBCL) will be the two most common types. On average, each year, 15 000 new cases of FL are diagnosed in the United States alone. Despite dramatic improvements worldwide in the treatment of FL, such as the emergence of anti-CD20 agents, FL cannot be cured yet. There is no widely agreed standard of care for the first line therapy of FL. Current options include “watch and wait” strategies, rituximab monotherapy, multi-drug therapy of rituximab and bendamustine or CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone), CVP (cyclophosphamide, vincristine, prednisones), or combinations with the new anti-CD 20 monoclonal antibody obinutuzumab. Even with average of 80% response rate to initial therapy 20% of patients relapse within 2 years and there is no clear consensus on further management. However, a diverse set of new drugs with different mechanisms of action are available in a relapse setting. These drugs have extended overall survival (OS) up to 12 years. An indolent course of FL is manifested by varying periods of remissions and relapses that can potentially progress to transformation into either other hematologic malignancy (eg, DLBCL) or become chemo-refractory. Considering the chronic nature of FL, physicians should strive for both efficacy of treatment and possible extended-length remissions, and for good patient quality of life and limited toxicity.","PeriodicalId":72084,"journal":{"name":"Advances in cell and gene therapy","volume":"3 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/acg2.74","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42653373","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

Cancer-associated thrombosis: Where do we stand? 癌症相关血栓:我们在哪里?

Advances in cell and gene therapy Pub Date : 2019-07-27 DOI: 10.1002/acg2.73

Hanny Al-Samkari, Andrew B. Song, Jean M. Connors

{"title":"Cancer-associated thrombosis: Where do we stand?","authors":"Hanny Al-Samkari, Andrew B. Song, Jean M. Connors","doi":"10.1002/acg2.73","DOIUrl":"10.1002/acg2.73","url":null,"abstract":"Venous thromboembolism (VTE) is a major cause of morbidity and mortality in cancer patients. Cancer patients have a four to sevenfold increased risk of VTE compared with non-cancer patients and approximately 20%-30% of all VTE occurs in patients with cancer. Numerous clinical and biologic risk factors predispose cancer patients to VTE, including cancer-directed treatments, tumor site of origin, and circulating mediators produced by tumor cells. Along with clinical risk factors, measurable markers of increased risk such as elevations of the platelet or leukocyte counts, soluble P-selectin, and D-dimer have been integrated to develop numerous risk stratification scores to predict those patients at high risk for cancer-associated VTE. Utilizing risk stratification models, recent studies have examined the use of direct oral anticoagulants (DOACs) for primary thromboprophylaxis of VTE, with promising results. Treatment of cancer-associated VTE is currently evolving. The long-accepted standard of care, low molecular weight heparin (LMWH), is currently being compared with the DOACs in clinical trials. Trials to date using edoxaban and rivaroxaban have found that DOACs are non-inferior to LMWH for the secondary prevention of cancer-associated VTE but may result in an increased rate of bleeding, especially in certain patient groups. Additional studies are ongoing and will be necessary to further define optimal VTE treatment for many cancer patient subpopulations.","PeriodicalId":72084,"journal":{"name":"Advances in cell and gene therapy","volume":"3 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-07-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/acg2.73","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43479764","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: 4

Future prospects of chimeric antigen receptor T-cell therapy for multiple myeloma 嵌合抗原受体t细胞治疗多发性骨髓瘤的前景展望

Advances in cell and gene therapy Pub Date : 2019-07-05 DOI: 10.1002/acg2.72

Carlos Fernandez de Larrea, Sham Mailankody, Ola Landgren, Eric L. Smith

{"title":"Future prospects of chimeric antigen receptor T-cell therapy for multiple myeloma","authors":"Carlos Fernandez de Larrea, Sham Mailankody, Ola Landgren, Eric L. Smith","doi":"10.1002/acg2.72","DOIUrl":"10.1002/acg2.72","url":null,"abstract":"Although multiple myeloma (MM) remains an incurable hematological malignancy, the introduction of autologous stem cell transplantation, proteasome inhibitors, and immunomodulatory agents has increased the survival of patients. However, most patients will become refractory to available therapeutic regimens. Moreover, conventional strategies have shown limited benefit in high-risk patients with adverse cytogenetics. Therefore, novel strategies including immunotherapy are needed to improve the outcomes of these patients. Immunotherapy includes a range of strategies to redirect the immune system to attack tumor cells. Here, we review the most promising immunotherapy strategy published to date for many hematologic malignancies, chimeric antigen receptor (CAR) T cells. Most clinical studies of CAR T cell therapy for MM target B-cell maturation antigen (BCMA) on malignant plasma cells. The initial studies using BCMA targeted CAR T cells are devoted to patients with advanced relapsed/refractory MM. Eventual relapse after CAR T-cell therapy remains an issue. We present the most recent clinical data, as well as relevant preclinical data demonstrating novel strategies with the potential to improve clinical outcomes of cellular therapy for MM. Further, we present a proposal for how CAR T-cell therapy may fit into the future therapeutic landscape of MM as adoptive cellular therapy moves beyond the currently studied multiply relapsed/refractory setting.","PeriodicalId":72084,"journal":{"name":"Advances in cell and gene therapy","volume":"3 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-07-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/acg2.72","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42706405","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

Minimal residual disease in multiple myeloma 2019 多发性骨髓瘤极小残留病变2019

Advances in cell and gene therapy Pub Date : 2019-06-25 DOI: 10.1002/acg2.71

Chutima Kunacheewa, Pei Lin, Elisabet E. Manasanch

引用次数: 3