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  • 1
    Language: English
    In: Bone marrow transplantation (Basingstoke), 2008-01, Vol.41 (2), p.207-214
    Description: The use of alternative hematopoietic stem cell (HSC) donors has been witnessing important progress, mainly due to: (i) better HLA matching at the allelic level between donor and recipient in unrelated HSC transplantation (HSCT) translating into better patient outcome; (ii) better donor choice and patient selection in unrelated, often HLA-mismatched, cord blood transplantation and (iii) new strategies of adoptive cell therapy aimed at improving the results of T-cell-depleted haploidentical HSCT from a relative. Currently, it is possible to find an HSC donor for virtually almost all children with an indication to receive allogeneic HSCT and lacking an HLA-identical sibling. Each of the three options of HSCT from alternative donors has advantages and limitations. Therefore, any physician has to carefully evaluate, for each single pediatric patient in need of an allograft, all the possible alternatives to choose the best HSC donor, taking into account type of disease to be treated, urgency of transplantation, donor characteristics and center's experience. This review will analyze in detail the advantages and limitations of each of the three options of alternative donor HSCT and the main criteria to be used for choosing the most suitable donor for pediatric patients lacking an HLA-identical sibling.
    Subject(s): Histocompatibility Testing ; Humans ; Hematopoietic Stem Cell Transplantation - adverse effects ; Survival Analysis ; Child, Preschool ; Hematopoietic Stem Cell Transplantation - methods ; Lymphocyte Depletion ; Tissue Donors ; Cord Blood Stem Cell Transplantation ; Graft vs Host Disease ; Transplantation, Homologous - adverse effects ; Transplantation, Homologous - methods ; Usage ; Patient outcomes ; Physiological aspects ; Transplantation ; Organ donors ; Health aspects ; Histocompatibility testing ; Methods ; Hematopoietic stem cells ; Index Medicus
    ISSN: 0268-3369
    E-ISSN: 1476-5365
    Source: Nature Open Access
    Source: Academic Search Ultimate
    Source: Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals
    Source: Alma/SFX Local Collection
    Source: © ProQuest LLC All rights reserved〈img src="https://exlibris-pub.s3.amazonaws.com/PQ_Logo.jpg" style="vertical-align:middle;margin-left:7px"〉
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  • 2
    Language: English
    In: Bone marrow transplantation (Basingstoke), 2012, Vol.47 (2), p.164-171
    Description: Because of their immunomodulatory and engraftment-promoting properties, mesenchymal stromal cells (MSCs) have been tested in the clinical setting both to facilitate haematopoietic recovery and to treat steroid-resistant acute GVHD. More recently, experimental findings and clinical trials have focused on the ability of MSCs to home to damaged tissue and to produce paracrine factors with anti-inflammatory properties, resulting in functional recovery of the damaged tissue. The mechanisms through which MSCs exert their therapeutic potential rely on some key properties of the cells: the ability to secrete soluble factors capable of stimulating survival and recovery of injured cells; the capacity to home to sites of damage and the ability to blunt exaggerated immune responses. These fundamental properties are being tested within a novel therapeutic field defined as Regenerative Medicine. This review deals with recent research on the anti-inflammatory/reparative properties of MSCs and considers the possible mechanisms of function responsible for these effects. Moreover, current and potential clinical applications of MSC-based treatment strategies in the context of Regenerative Medicine are being discussed. Key issues such as optimal timing of MSC administration, cell dose and schedule of administration, advantages and disadvantages of using autologous or allogeneic cells are still open. Nonetheless, MSCs promise to represent a revolution for many severe or presently untreatable disorders.
    Subject(s): Biological and medical sciences ; Medical sciences ; Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy ; Bone marrow, stem cells transplantation. Graft versus host reaction ; Transfusions. Complications. Transfusion reactions. Cell and gene therapy ; Mesenchymal Stem Cell Transplantation - methods ; Mesenchymal Stromal Cells - cytology ; Animals ; Regenerative Medicine - methods ; Humans ; Care and treatment ; Systemic lupus erythematosus ; Stem cells ; Bone marrow ; Transplantation ; Research ; Health aspects ; Index Medicus
    ISSN: 0268-3369
    E-ISSN: 1476-5365
    Source: Nature Open Access
    Source: Academic Search Ultimate
    Source: Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals
    Source: Alma/SFX Local Collection
    Source: © ProQuest LLC All rights reserved〈img src="https://exlibris-pub.s3.amazonaws.com/PQ_Logo.jpg" style="vertical-align:middle;margin-left:7px"〉
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  • 3
    Language: English
    In: British journal of pharmacology, 2015-11, Vol.172 (21), p.5025-5036
    Description: Intravenous (IV) iron therapy is widely used in iron deficiency anaemias when oral iron is not tolerated or ineffective. Administration of IV‐iron is considered a safe procedure, but severe hypersensitivity reactions (HSRs) can occur at a very low frequency. Recently, new guidelines have been published by the European Medicines Agency with the intention of making IV‐iron therapy safer; however, the current protocols are still non‐specific, non‐evidence‐based empirical measures which neglect the fact that the majority of IV‐iron reactions are not IgE‐mediated anaphylactic reactions. The field would benefit from new specific and effective methods for the prevention and treatment of these HSRs, and the main goal of this review was to highlight a possible new approach based on the assumption that IV‐iron reactions represent complement activation‐related pseudo‐allergy (CARPA), at least in part. The review compares the features of IV‐iron reactions to those of immune and non‐immune HSRs caused by a variety of other infused drugs and thus make indirect inferences on IV‐iron reactions. The process of comparison highlights many unresolved issues in allergy research, such as the unsettled terminology, multiple redundant classifications and a lack of validated animal models and lege artis clinical studies. Facts and arguments are listed in support of the involvement of CARPA in IV‐iron reactions, and the review addresses the mechanism of low reactogenic administration protocols (LRPs) based on slow infusion. It is suggested that consideration of CARPA and the use of LRPs might lead to useful new additions to the management of high‐risk IV‐iron patients.
    Subject(s): Iron - administration & dosage ; Drug Hypersensitivity - classification ; Anemia, Iron-Deficiency - drug therapy ; Humans ; Infusions, Intravenous ; Iron - adverse effects ; Drug Hypersensitivity - therapy ; Allergy ; Terms and phrases ; Allergic reaction ; Analysis ; Index Medicus ; Review
    ISSN: 0007-1188
    E-ISSN: 1476-5381
    Source: Academic Search Ultimate
    Source: Wiley Online Library All Journals
    Source: PubMed Central
    Source: Alma/SFX Local Collection
    Source: © ProQuest LLC All rights reserved〈img src="https://exlibris-pub.s3.amazonaws.com/PQ_Logo.jpg" style="vertical-align:middle;margin-left:7px"〉
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  • 4
    Language: English
    In: Bone marrow transplantation (Basingstoke), 2018-02, Vol.53 (2), p.138-145
    Description: The advances in hematopoietic cell transplantation (HCT) over the last decade have led to a transplant-related mortality below 15%. Hepatic sinusoidal obstruction syndrome/veno-occlusive disease (SOS/VOD) is a life-threatening complication of HCT that belongs to a group of diseases increasingly identified as transplant-related, systemic endothelial diseases. In most cases, SOS/VOD resolves within weeks; however, severe SOS/VOD results in multi-organ dysfunction/failure with a mortality rate 〉80%. A timely diagnosis of SOS/VOD is of critical importance, given the availability of therapeutic options with favorable tolerability. Current diagnostic criteria are used for adults and children. However, over the last decade it has become clear that SOS/VOD is significantly different between the age groups in terms of incidence, genetic predisposition, clinical presentation, prevention, treatment and outcome. Improved understanding of SOS/VOD and the availability of effective treatment questions the use of the Baltimore and Seattle criteria for diagnosing SOS/VOD in children. The aim of this position paper is to propose new diagnostic and severity criteria for SOS/VOD in children on behalf of the European Society for Blood and Marrow Transplantation.
    Subject(s): Europe ; Humans ; Risk Factors ; Female ; Male ; Treatment Outcome ; Hepatic Veno-Occlusive Disease - classification ; Hepatic Veno-Occlusive Disease - diagnosis ; Hepatic Veno-Occlusive Disease - pathology ; Incidence ; Usage ; Care and treatment ; Transplantation ; Children ; Diagnosis ; Hematopoietic stem cells ; Diseases ; Index Medicus ; Special Report ; Clinical Medicine ; Pediatrics ; Hematologi ; Medical and Health Sciences ; Hematology ; Medicin och hälsovetenskap ; Pediatrik ; Klinisk medicin
    ISSN: 0268-3369
    E-ISSN: 1476-5365
    Source: Nature Open Access
    Source: Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals
    Source: Alma/SFX Local Collection
    Source: © ProQuest LLC All rights reserved〈img src="https://exlibris-pub.s3.amazonaws.com/PQ_Logo.jpg" style="vertical-align:middle;margin-left:7px"〉
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  • 5
    Language: English
    In: Oncogene, 2013-02-21, Vol.32 (8), p.998-1009
    Description: Grade IV astrocytoma or glioblastoma multiforme (GBM) is one of the most aggressive and lethal tumors affecting humans. ADAR2-mediated A-to-I RNA editing, an essential post-transcriptional modification event in brain, is impaired in GBMs and astrocytoma cell lines. However, the role of ADAR2 editing in astrocytomas remains to be defined. Here, we show that ADAR2 editing rescue in astrocytomas prevents tumor growth in vivo and modulates an important cell cycle pathway involving the Skp2/p21/p27 proteins, often altered in glioblastoma. We demonstrate that ADAR2 deaminase activity is essential to inhibit tumor growth. Indeed, we identify the phosphatase CDC14B, which acts upstream of the Skp2/p21/p27 pathway, as a novel and critical ADAR2 target gene involved in glioblastoma growth. Specifically, ADAR2-mediated editing on CDC14B pre-mRNA increases its expression with a consequent reduction of the Skp2 target protein, as shown both in vitro and in vivo. We found that, compared to normal brain, both CDC14B editing and expression are progressively impaired in astrocytomas from grade I to IV, being very low in GBMs. These findings (1) demonstrate that post-transcriptional A-to-I RNA editing might be crucial for glioblastoma pathogenesis, (2) identify ADAR2-editing enzyme as a novel candidate tumor suppressor gene and (3) provide proof of principle that ADAR2 or its substrates may represent a suitable target(s) for possible novel, more effective and less toxic approaches to the treatment of GBMs.
    Subject(s): Astrocytoma - genetics ; Astrocytoma - metabolism ; RNA-Binding Proteins - genetics ; Brain Neoplasms - enzymology ; Adenosine Deaminase - genetics ; Adenosine Deaminase - metabolism ; Dual-Specificity Phosphatases - metabolism ; Humans ; Brain Neoplasms - pathology ; Brain Neoplasms - genetics ; Cell Growth Processes - physiology ; Transplantation, Heterologous ; S-Phase Kinase-Associated Proteins - metabolism ; Brain Neoplasms - metabolism ; Cyclin-Dependent Kinase Inhibitor p27 - metabolism ; Astrocytoma - pathology ; Animals ; Transfection ; Mice, Nude ; Cyclin-Dependent Kinase Inhibitor p21 - metabolism ; Astrocytoma - enzymology ; Female ; Mice ; RNA-Binding Proteins - metabolism ; Physiological aspects ; Research ; Adenosine deaminase ; Growth ; Glioblastoma multiforme ; RNA editing ; GBM ; cell cycle ; Original ; ADAR2 ; CDC14B
    ISSN: 0950-9232
    E-ISSN: 1476-5594
    Source: Nature Open Access
    Source: Academic Search Ultimate
    Source: Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals
    Source: Alma/SFX Local Collection
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  • 6
    Language: English
    In: Oncogene, 2014-08-07, Vol.33 (32), p.4173-4184
    Description: The Polycomb group (PcG) proteins regulate stem cell differentiation via the repression of gene transcription, and their deregulation has been widely implicated in cancer development. The PcG protein Enhancer of Zeste Homolog 2 (EZH2) works as a catalytic subunit of the Polycomb Repressive Complex 2 (PRC2) by methylating lysine 27 on histone H3 (H3K27me3), a hallmark of PRC2-mediated gene repression. In skeletal muscle progenitors, EZH2 prevents an unscheduled differentiation by repressing muscle-specific gene expression and is downregulated during the course of differentiation. In rhabdomyosarcoma (RMS), a pediatric soft-tissue sarcoma thought to arise from myogenic precursors, EZH2 is abnormally expressed and its downregulation in vitro leads to muscle-like differentiation of RMS cells of the embryonal variant. However, the role of EZH2 in the clinically aggressive subgroup of alveolar RMS, characterized by the expression of PAX3-FOXO1 oncoprotein, remains unknown. We show here that EZH2 depletion in these cells leads to programmed cell death. Transcriptional derepression of F-box protein 32 (FBXO32) (Atrogin1/MAFbx), a gene associated with muscle homeostasis, was evidenced in PAX3-FOXO1 RMS cells silenced for EZH2. This phenomenon was associated with reduced EZH2 occupancy and H3K27me3 levels at the FBXO32 promoter. Simultaneous knockdown of FBXO32 and EZH2 in PAX3-FOXO1 RMS cells impaired the pro-apoptotic response, whereas the overexpression of FBXO32 facilitated programmed cell death in EZH2-depleted cells. Pharmacological inhibition of EZH2 by either 3-Deazaneplanocin A or a catalytic EZH2 inhibitor mirrored the phenotypic and molecular effects of EZH2 knockdown in vitro and prevented tumor growth in vivo. Collectively, these results indicate that EZH2 is a key factor in the proliferation and survival of PAX3-FOXO1 alveolar RMS cells working, at least in part, by repressing FBXO32. They also suggest that the reducing activity of EZH2 could represent a novel adjuvant strategy to eradicate high-risk PAX3-FOXO1 alveolar RMS.
    Subject(s): Cell Proliferation ; Humans ; Gene Expression Regulation, Neoplastic ; Homeostasis ; SKP Cullin F-Box Protein Ligases - physiology ; Male ; Cell Nucleus - metabolism ; Rhabdomyosarcoma, Alveolar - metabolism ; Forkhead Transcription Factors - metabolism ; Female ; Muscle Proteins - antagonists & inhibitors ; Cell Differentiation ; Child ; Muscle Proteins - physiology ; PAX3 Transcription Factor ; Cell Survival ; Gene Silencing ; SKP Cullin F-Box Protein Ligases - antagonists & inhibitors ; Enhancer of Zeste Homolog 2 Protein ; Histone-Lysine N-Methyltransferase - metabolism ; Adolescent ; Polycomb Repressive Complex 2 - physiology ; Cell Line, Tumor ; Forkhead Box Protein O1 ; Paired Box Transcription Factors - metabolism ; Apoptosis ; Cellular proteins ; Rhabdomyosarcoma ; Physiological aspects ; Development and progression ; Genetic aspects ; Genetic transcription ; Research ; Cell differentiation ; Index Medicus
    ISSN: 0950-9232
    E-ISSN: 1476-5594
    Source: Nature Open Access
    Source: Academic Search Ultimate
    Source: Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals
    Source: Alma/SFX Local Collection
    Source: © ProQuest LLC All rights reserved〈img src="https://exlibris-pub.s3.amazonaws.com/PQ_Logo.jpg" style="vertical-align:middle;margin-left:7px"〉
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  • 7
    Language: English
    In: Bone marrow transplantation (Basingstoke), 2016-04, Vol.51 (4), p.536-541
    Description: Allogeneic hemopoietic stem cell transplantation (HSCT) is the only method currently available to cure transfusion-dependent thalassemia major that has been widely used worldwide. To verify transplantation distribution, demography, activity, policies and outcomes inside the European Group for Blood and Marrow Transplantation (EBMT), we performed a retrospective non-interventional study, extracting data from the EBMT hemoglobinopathy prospective registry database. We included 1493 consecutive patients with thalassemia major transplanted between 1 January 2000 and 31 December 2010. In total, 1359 (91%) transplants were performed on patients 〈18 years old, 1061 were from a human leukocyte Ag-identical sibling donor. After a median observation time of 2 years, the 2-year overall survival (OS) and event-free survival (EFS; that is, thalassemia-free survival) were 88 ± 1% and 81 ± 1%, respectively. Transplantation from a human leukocyte Ag-identical sibling offered the best results, with OS and EFS of 91 ± 1% and 83 ± 1%, respectively. No significant differences in survival were reported between countries. The threshold age for optimal transplant outcomes was around 14 years, with an OS of 90-96% and an EFS of 83-93% when transplants were performed before this age. Allogeneic HSCT for thalassemia is a curative approach that is employed internationally and produces excellent results.
    Subject(s): Thalassemia - therapy ; Thalassemia - mortality ; Europe ; Humans ; Middle Aged ; Hematopoietic Stem Cell Transplantation ; Male ; Survival Rate ; Disease-Free Survival ; Societies, Medical ; Adolescent ; Adult ; Female ; Registries ; Bone marrow ; Thalassemia ; Care and treatment ; Transplantation ; Research ; Health aspects ; Index Medicus
    ISSN: 0268-3369
    E-ISSN: 1476-5365
    Source: Nature Open Access
    Source: Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals
    Source: Alma/SFX Local Collection
    Source: © ProQuest LLC All rights reserved〈img src="https://exlibris-pub.s3.amazonaws.com/PQ_Logo.jpg" style="vertical-align:middle;margin-left:7px"〉
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  • 8
    Language: English
    In: Annals of the rheumatic diseases, 2018-06, Vol.77 (Suppl 2), p.1519
    Description: BackgroundSkin ulcers are a frequent manifestation of systemic sclerosis (SSc). Skin ulcers are painful, represent a cause of disability and heavily affect patients’ quality of life. The presence of local infection may be responsible for osteomyelitis (OM) of the underlying bone. If gangrene develops, surgical amputation may be required. At the moment is not clear if there are predisposing factors to osteomyelitis development.ObjectivesTo describe a population of SSc patients affected by cutaneous ulcers and osteomyelitisMethodsWe collected data of SSc patients satisfying the 2013 ACR criteria for SSc referring to our outpatient clinic from January 1st 2016 to December 31st 2017. The patient’s data were evaluated on the basis of individual clinical records, including demographic, clinical and serological findings. Cutaneous ulcers were defined as epithelial loss and loss of dermis; post-traumatic skin lesions were excluded. In cases suspected of infection, microbiological investigations were carried out. We have diagnosed OM by clinical, radiological and laboratory means, in particular the presence of pain, swelling, fever, erythema, purulent secretions, blood chemistry alterations and typical radiological characteristics at either plain X ray and/or MRI. Statistical analysis was performed using STATA software for descriptive analysis and groups comparisons. Given the low number of events only univariate analysis was conducted.ResultsA total of 189 patients were enrolled in the study. Of them, 21 (11.1%) were males, mean age was 64.39±12.5 years and median disease duration 11.59 (5.6–19.3) years. A diffuse cutaneous (dcSSc) involvement was present in 50 (26.5%), limited cutaneous (lcSSc) in 131 (69.3%) and a limited disease in 8 patients (lSSC) (4.2%). Digital ulcers (DU) were present in 29 patients (15.3%) and in 5 cases (2.6%) were complicated by the occurrence of OM. The pathogens responsible of the infections were isolated in 3/5 (60%) cases and were represented by: Methicillin-sensitive Staphilococcus Aereus (2 cases) and P. Aeruginosa, also multisensitive. OM affected the third finger of right hand in 2 (40%) patients, the second finger of right hand in 1 (20%) patient and the third finger of left hand in 2 patients (40%). In 2 cases (40%) surgical amputation had to be performed. Patients with OM were significantly younger (54.9±16.07 vs 64.65±12.34, p 0.0432) and had higher CRP levels than the rest of the patients (1.27±0.59 vs 0.42±0.74, p 0.0061) In patients with DU, the only predictive factor for the development of OM was the total number of ulcers in the single patient (OR 2.27, 1.39–3.71, p〈0.001) while no significant influence was found for other demographical or disease specific parameter.ConclusionsOM is a severe complication of DU in SSc. In most cases the aetiologic agents are community-acquired pathogens. SSc patients with OM were younger but did not show any other obvious distinguishing feature. The number of ulcers in the single patients were predictive of OM development. Further and larger studies are needed to address this aspect of the microvascular involvement of SSc.Disclosure of InterestNone declared
    Subject(s): Pathogens ; Statistical analysis ; Finger ; Dermis ; Secretions ; Patients ; Hand ; Fever ; Quality of life ; Methicillin ; Osteomyelitis ; Pain ; Magnetic resonance imaging ; Systemic sclerosis ; Ulcers ; Amputation ; Gangrene ; Skin diseases ; Microvasculature ; Erythema
    ISSN: 0003-4967
    E-ISSN: 1468-2060
    Source: Alma/SFX Local Collection
    Source: © ProQuest LLC All rights reserved〈img src="https://exlibris-pub.s3.amazonaws.com/PQ_Logo.jpg" style="vertical-align:middle;margin-left:7px"〉
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  • 9
    Language: English
    In: Leukemia, 2015-02, Vol.29 (2), p.396-405
    Description: Hematopoietic stem cell transplantation (HSCT) from human leukocyte antigen (HLA) haploidentical family donors is a promising therapeutic option for high-risk hematologic malignancies. Here we explored in 121 patients, mostly with advanced stage diseases, a sirolimus-based, calcineurin-inhibitor-free prophylaxis of graft-versus-host disease (GvHD) to allow the infusion of unmanipulated peripheral blood stem cell (PBSC) grafts from partially HLA-matched family donors (TrRaMM study, Eudract 2007-5477-54). Conditioning regimen was based on treosulfan and fludarabine, and GvHD prophylaxis on antithymocyte globulin Fresenius (ATG-F), rituximab and oral administration of sirolimus and mycophenolate. Neutrophil and platelet engraftment occurred in median at 17 and 19 days after HSCT, respectively, and full donor chimerism was documented in patients' bone marrow since the first post-transplant evaluation. T-cell immune reconstitution was rapid, and high frequencies of circulating functional T-regulatory cells (Treg) were documented during sirolimus prophylaxis. Incidence of acute GvHD grade II-IV was 35%, and occurrence and severity correlated negatively with Treg frequency. Chronic GvHD incidence was 47%. At 3 years after HSCT, transpant-related mortality was 31%, relapse incidence 48% and overall survival 25%. In conclusion, GvHD prophylaxis with sirolimus-mycophenolate-ATG-F-rituximab promotes a rapid immune reconstitution skewed toward Tregs, allowing the infusion of unmanipulated haploidentical PBSC grafts.
    Subject(s): Busulfan - analogs & derivatives ; Neutrophils - cytology ; Prospective Studies ; Humans ; Immunosuppressive Agents - therapeutic use ; Middle Aged ; Male ; Graft vs Host Disease - immunology ; T-Lymphocytes, Regulatory - immunology ; Young Adult ; Blood Platelets - cytology ; Antilymphocyte Serum - therapeutic use ; Adult ; Female ; Child ; Sirolimus - therapeutic use ; Busulfan - therapeutic use ; Administration, Oral ; HLA Antigens - immunology ; Rituximab ; Treatment Outcome ; Vidarabine - analogs & derivatives ; Vidarabine - therapeutic use ; Mycophenolic Acid - analogs & derivatives ; Mycophenolic Acid - therapeutic use ; Adolescent ; Graft vs Host Disease - prevention & control ; T-Lymphocytes - immunology ; Aged ; Tissue Donors ; Transplantation Conditioning ; Peripheral Blood Stem Cell Transplantation ; Antibodies, Monoclonal, Murine-Derived - therapeutic use ; Prevention ; Complications and side effects ; Care and treatment ; Graft versus host reaction ; Transplantation ; T cells ; Blood diseases ; Health aspects ; Hematopoietic stem cells ; Research ; Drug therapy ; Risk factors ; Index Medicus
    ISSN: 0887-6924
    E-ISSN: 1476-5551
    Source: Nature Open Access
    Source: Academic Search Ultimate
    Source: Alma/SFX Local Collection
    Source: © ProQuest LLC All rights reserved〈img src="https://exlibris-pub.s3.amazonaws.com/PQ_Logo.jpg" style="vertical-align:middle;margin-left:7px"〉
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  • 10
    Language: English
    In: Leukemia, 2020-04, Vol.34 (4), p.1102-1115
    Description: We developed an innovative and efficient, feeder-free culture method to genetically modify and expand peripheral blood-derived NK cells with high proliferative capacity, while preserving the responsiveness of their native activating receptors. Activated peripheral blood NK cells were efficiently transduced by a retroviral vector, carrying a second-generation CAR targeting CD19. CAR expression was demonstrated across the different NK-cell subsets. CAR.CD19-NK cells display higher antileukemic activity toward CD19 cell lines and primary blasts obtained from patients with B-cell precursor ALL compared with unmodified NK cells. In vivo animal model data showed that the antileukemia activity of CAR.CD19-NK cell is superimposable to that of CAR-T cells, with a lower xenograft toxicity profile. These data support the feasibility of generating feeder-free expanded, genetically modified peripheral blood NK cells for effective "off-the-shelf" immuno-gene-therapy, while their innate alloreactivity can be safely harnessed to potentiate allogeneic cell therapy.
    Subject(s): Cell- and Tissue-Based Therapy - methods ; Killer Cells, Natural - transplantation ; Immunotherapy, Adoptive - methods ; Precursor B-Cell Lymphoblastic Leukemia-Lymphoma - pathology ; Cell Proliferation ; Humans ; Mice, SCID ; Precursor B-Cell Lymphoblastic Leukemia-Lymphoma - therapy ; Precursor B-Cell Lymphoblastic Leukemia-Lymphoma - immunology ; Xenograft Model Antitumor Assays ; Animals ; Leukocytes, Mononuclear - immunology ; Receptors, Chimeric Antigen - immunology ; Killer Cells, Natural - immunology ; Mice, Inbred NOD ; Mice ; Tumor Cells, Cultured ; Cytotoxicity, Immunologic - immunology ; Antigens, CD19 - immunology ; Apoptosis ; Cell culture ; Killer cells ; Usage ; Care and treatment ; Growth ; Cellular therapy ; Acute lymphocytic leukemia ; Methods ; Index Medicus
    ISSN: 0887-6924
    E-ISSN: 1476-5551
    Source: Nature Open Access
    Source: Alma/SFX Local Collection
    Source: © ProQuest LLC All rights reserved〈img src="https://exlibris-pub.s3.amazonaws.com/PQ_Logo.jpg" style="vertical-align:middle;margin-left:7px"〉
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