Abstract:
:Umbilical cord blood (CB) has emerged as an effective alternative donor source for hematopoietic stem cell transplantation. Despite this success, the prolonged duration of immune suppression following CB transplantation and the naiveté of CB T cells leave patients susceptible to viral infections. Adoptive transfer of ex vivo-expanded virus-specific T cells from CB is both feasible and safe. However, the manufacturing process of these cells is complicated, lengthy, and labor-intensive. We have now developed a simplified method to manufacture a single culture of polyclonal multivirus-specific cytotoxic T cells in less than 30 days. It eliminates the need for a live virus or transduction with a viral vector, thus making this approach widely available and GMP-applicable to target multiple viruses. The use of overlapping PepMixes as a source of antigen stimulation enable expansion of the repertoire of the T cell product to any virus of interest and make it available as a third party "off the shelf" treatment for viral infections following transplantation.
journal_name
Mol Ther Methods Clin Devjournal_title
Molecular therapy. Methods & clinical developmentauthors
Dave H,Luo M,Blaney JW,Patel S,Barese C,Cruz CR,Shpall EJ,Bollard CM,Hanley PJdoi
10.1016/j.omtm.2017.02.001subject
Has Abstractpub_date
2017-03-08 00:00:00pages
13-21issn
2329-0501pii
S2329-0501(17)30041-4journal_volume
5pub_type
杂志文章abstract::Pompe disease (PD) is a lysosomal disorder caused by acid α-glucosidase (GAA) deficiency. Progressive muscular weakness is the major symptom of PD, and enzyme replacement therapy can improve the clinical outcome. However, to achieve a better clinical outcome, alternative therapeutic strategies are being investigated, ...
journal_title:Molecular therapy. Methods & clinical development
pub_type: 杂志文章
doi:10.1038/mtm.2016.54
更新日期:2016-08-10 00:00:00
abstract::Gene therapy has been shown to be a feasible approach to treat inherited disorders in vivo. Among the currently used viral vector systems, adeno-associated virus (AAV) vectors are the most advanced and have been applied in patients successfully. An important drawback of non-integrating AAV vectors is their loss of exp...
journal_title:Molecular therapy. Methods & clinical development
pub_type: 杂志文章
doi:10.1016/j.omtm.2018.02.010
更新日期:2018-02-27 00:00:00
abstract::Herpes simplex keratitis (HSK) is the most common cause of corneal blindness in developed nations, caused by primary or recurrent herpes simplex virus 1 (HSV-1) infection of the cornea. Latent infection of HSV-1, especially in the trigeminal ganglion (TG), causes recurrence of HSV-1 infection. As antiviral treatment i...
journal_title:Molecular therapy. Methods & clinical development
pub_type: 杂志文章
doi:10.1016/j.omtm.2020.05.011
更新日期:2020-05-22 00:00:00
abstract::There is no effective serologic parameter to distinguish different types of pancreatitis now. To distinguish between acute pancreatitis (AP) and acute exacerbations of chronic pancreatitis (CP) and to determine whether fibrosis occurs in CP, we evaluated the ability to produce white blood cells (WBCs), the neutrophil-...
journal_title:Molecular therapy. Methods & clinical development
pub_type: 杂志文章
doi:10.1016/j.omtm.2020.05.010
更新日期:2020-05-22 00:00:00
abstract::Possible risks and lack of donor livers limit application of liver transplantation. Liver cell transplantation is, at this moment, not a feasible alternative because engraftment in the liver is poor. Furthermore, there is also shortage of cells suitable for transplantation. Fetal liver cells are able to proliferate in...
journal_title:Molecular therapy. Methods & clinical development
pub_type: 杂志文章
doi:10.1038/mtm.2014.3
更新日期:2014-03-12 00:00:00
abstract::Current cell processing technologies for gene and cell therapies are often slow, expensive, labor intensive and are compromised by high cell losses and poor selectivity thus limiting the efficacy and availability of clinical cell therapies. We employ cell-specific on-demand mechanical intracellular impact from laser p...
journal_title:Molecular therapy. Methods & clinical development
pub_type: 杂志文章
doi:10.1038/mtm.2016.12
更新日期:2016-03-16 00:00:00
abstract::Pompe disease is an autosomal recessive lysosomal storage disorder characterized by progressive muscle weakness. The disease is caused by mutations in the acid α-glucosidase (GAA) gene. Despite the currently available enzyme replacement therapy (ERT), roughly half of the infants with Pompe disease die before the age o...
journal_title:Molecular therapy. Methods & clinical development
pub_type: 杂志文章
doi:10.1016/j.omtm.2020.04.023
更新日期:2020-05-04 00:00:00
abstract::Adeno-associated virus (AAV) vector serotypes vary in their ability to transduce hepatocytes from different species. Chimeric mouse models harboring human hepatocytes have shown translational promise for liver-directed gene therapies. However, many variables that influence human hepatocyte transduction and transgene e...
journal_title:Molecular therapy. Methods & clinical development
pub_type: 杂志文章
doi:10.1016/j.omtm.2020.05.033
更新日期:2020-06-02 00:00:00
abstract::Validation of gene transfer vectors containing tissue-specific promoters in cell-based functional assays poses a formidable challenge for gene therapy product development. Here, we describe a novel approach based on CRISPR/dCas9 transcriptional activation to achieve robust transgene expression from transgene cassettes...
journal_title:Molecular therapy. Methods & clinical development
pub_type: 杂志文章
doi:10.1016/j.omtm.2019.03.004
更新日期:2019-03-28 00:00:00
abstract::Type 1 diabetes affects 20 million patients worldwide. Insulin is the primary and commonly the sole therapy for type 1 diabetes. However, only a minority of patients attain the targeted glucose control and reduced adverse events. We tested urocortin 2 gene transfer as single-agent therapy for insulin deficiency using ...
journal_title:Molecular therapy. Methods & clinical development
pub_type: 杂志文章
doi:10.1016/j.omtm.2019.12.002
更新日期:2019-12-14 00:00:00
abstract::Lentiviral vectors have emerged as an efficient, safe therapeutic tool for gene therapy based on hematopoietic stem cells (HSCs) or T cells. However, the monitoring of transduced cells in preclinical models remains challenging because of the inefficient transduction of murine primary T cells with lentiviral vectors, i...
journal_title:Molecular therapy. Methods & clinical development
pub_type: 杂志文章
doi:10.1016/j.omtm.2018.08.002
更新日期:2018-08-08 00:00:00
abstract::Spinal muscular atrophy (SMA) is a devastating childhood motor neuron disease. SMA is caused by mutations in the survival motor neuron gene (SMN1), leading to reduced levels of SMN protein in the CNS. The actin-binding protein plastin 3 (PLS3) has been reported as a modifier for SMA, making it a potential therapeutic ...
journal_title:Molecular therapy. Methods & clinical development
pub_type: 杂志文章
doi:10.1016/j.omtm.2018.01.007
更新日期:2018-01-31 00:00:00
abstract::Recombinant adeno-associated virus (rAAV) is currently the best vector for gene delivery into the skeletal muscle. However, the 5-kb packaging size of this virus is a major obstacle for large gene transfer. This past decade, many different strategies were developed to circumvent this issue (concatemerization-splicing,...
journal_title:Molecular therapy. Methods & clinical development
pub_type: 杂志文章
doi:10.1038/mtm.2015.9
更新日期:2015-03-25 00:00:00
abstract::Hypoxic regions within the tumor form due to imbalances between cell proliferation and angiogenesis; specifically, temporary closure or a reduced flow due to abnormal vasculature. They create environments where cancer cells acquire resistance to therapies. Therefore, the development of therapeutic approaches targeting...
journal_title:Molecular therapy. Methods & clinical development
pub_type: 杂志文章
doi:10.1038/mtm.2016.9
更新日期:2016-03-02 00:00:00
abstract::Insertional mutagenesis has been associated with malignant cell transformation in gene therapy protocols, leading to discussions about vector security. Therefore, clonal analysis is important for the assessment of vector safety and its impact on patient health. Here, we report a unique approach to assess dynamic chang...
journal_title:Molecular therapy. Methods & clinical development
pub_type: 杂志文章
doi:10.1038/mtm.2014.52
更新日期:2014-11-19 00:00:00
abstract::The overall goal of our research is to establish a preformed molecular guidance pathway to direct the growth of dopaminergic axons from embryonic ventral mesencephalon (VM), tissue placed within the substantia nigra (SN), into the striatum to reconstruct the nigrostriatal pathway in a hemi-Parkinson's disease rat mode...
journal_title:Molecular therapy. Methods & clinical development
pub_type: 杂志文章
doi:10.1016/j.omtm.2019.06.008
更新日期:2019-07-11 00:00:00
abstract::[This corrects the article DOI: 10.1038/mtm.2015.16.]. ...
journal_title:Molecular therapy. Methods & clinical development
pub_type: 已发布勘误
doi:10.1038/mtm.2016.32
更新日期:2016-05-25 00:00:00
abstract::New methods to produce large numbers of myeloid progenitor cells, precursors to macrophages (MΦs), by maintaining Hoxb8 transcription factor activity1 has reinvigorated interest in MΦ cell therapies. We generated Hoxb8-dependent myeloid progenitors (HDPs) by transducing lineage-negative bone marrow cells with a consti...
journal_title:Molecular therapy. Methods & clinical development
pub_type: 杂志文章
doi:10.1016/j.omtm.2017.08.007
更新日期:2017-09-07 00:00:00
abstract::Hemophilia A, caused by a deficiency in factor VIII (FVIII), is the most severe inherited bleeding disorder. Hemophilia A is an attractive gene therapy candidate because even small increases in FVIII levels will positively alter the phenotype. While several vectors are under investigation, gene addition from an integr...
journal_title:Molecular therapy. Methods & clinical development
pub_type: 杂志文章
doi:10.1038/mtm.2014.42
更新日期:2014-09-10 00:00:00
abstract::Gene replacement therapies, like organ and cell transplantation are likely to introduce neo-antigens that elicit rejection via humoral and/or effector T cell immune responses. Nonetheless, thanks to an ever growing body of pre-clinical studies it is now well accepted that gene transfer protocols can be specifically de...
journal_title:Molecular therapy. Methods & clinical development
pub_type: 杂志文章
doi:10.1038/mtm.2014.13
更新日期:2014-04-30 00:00:00
abstract::Because many peptide and peptide-mimetic drugs are substrates of peptide transporter 1, it is important to evaluate the peptide transporter 1-mediated intestinal absorption of drug candidates in the early phase of drug development. Although intestinal cell lines treated with inhibitors of peptide transporter 1 are wid...
journal_title:Molecular therapy. Methods & clinical development
pub_type: 杂志文章
doi:10.1016/j.omtm.2019.11.008
更新日期:2019-11-21 00:00:00
abstract::The marketing approval of genetically engineered hematopoietic stem cells (HSCs) as the first-line therapy for the treatment of severe combined immunodeficiency due to adenosine deaminase deficiency (ADA-SCID) is a tribute to the substantial progress that has been made regarding HSC engineering in the past decade. Rep...
journal_title:Molecular therapy. Methods & clinical development
pub_type: 杂志文章,评审
doi:10.1016/j.omtm.2017.03.003
更新日期:2017-03-18 00:00:00
abstract::Retroviral vectors, including those derived from gammaretroviruses and lentiviruses, have found their way into the clinical arena and demonstrated remarkable efficacy for the treatment of immunodeficiencies, leukodystrophies, and globinopathies. Despite these successes, gene therapy unfortunately also has had to face ...
journal_title:Molecular therapy. Methods & clinical development
pub_type: 杂志文章,评审
doi:10.1016/j.omtm.2017.10.002
更新日期:2017-10-05 00:00:00
abstract::Crigler-Najjar syndrome is a severe metabolic disease of the liver due to a reduced activity of the UDP Glucuronosyltransferase 1A1 (UGT1A1) enzyme. In an effort to translate to the clinic an adeno-associated virus vector mediated liver gene transfer approach to treat Crigler-Najjar syndrome, we developed and optimize...
journal_title:Molecular therapy. Methods & clinical development
pub_type: 杂志文章
doi:10.1038/mtm.2016.49
更新日期:2016-07-20 00:00:00
abstract::Sanfilippo syndrome type B (mucopolysaccharidosis type IIIB [MPS IIIB]) is a lysosomal storage disorder primarily affecting the brain that is caused by a deficiency in the enzyme α-N-acetylglucosaminidase (NAGLU), leading to intralysosomal accumulation of heparan sulfate. There are currently no treatments for this dis...
journal_title:Molecular therapy. Methods & clinical development
pub_type: 杂志文章
doi:10.1016/j.omtm.2018.06.005
更新日期:2018-07-23 00:00:00
abstract::Preventing untoward immune responses against a specific antigen is a major challenge in different clinical settings such as gene therapy, transplantation, or autoimmunity. Following intramuscular delivery of recombinant adeno-associated virus (rAAV)-derived vectors, transgene rejection can be a roadblock to successful...
journal_title:Molecular therapy. Methods & clinical development
pub_type: 杂志文章
doi:10.1038/mtm.2014.28
更新日期:2014-07-23 00:00:00
abstract::Recombinant adeno-associated virus (rAAV)rh74.MCK.GALGT2 is a muscle-specific gene therapy that is being developed to treat forms of muscular dystrophy. Here we report on an isolated limb infusion technique in a non-human primate model, where hindlimb blood flow is transiently isolated using balloon catheters to conce...
journal_title:Molecular therapy. Methods & clinical development
pub_type: 杂志文章
doi:10.1016/j.omtm.2018.06.002
更新日期:2018-07-14 00:00:00
abstract::Methods for customizing and improving virus vector tropism are limited. In this study, we introduce a microRNA (miRNA)-regulated molecular method to enhance vector transduction without genome alteration. Based on the importance of adenovirus (Ad) vectors for cancer and gene treatment, we exemplified this technology fo...
journal_title:Molecular therapy. Methods & clinical development
pub_type: 杂志文章
doi:10.1016/j.omtm.2020.06.010
更新日期:2020-06-18 00:00:00
abstract::The advent of RNA-guided endonuclease (RGEN)-mediated gene editing, specifically via CRISPR/Cas9, has spurred intensive efforts to improve the efficiency of both RGEN delivery and targeted mutagenesis. The major viral vectors in use for delivery of Cas9 and its associated guide RNA, lentiviral and adeno-associated vir...
journal_title:Molecular therapy. Methods & clinical development
pub_type: 杂志文章
doi:10.1038/mtm.2016.57
更新日期:2016-08-24 00:00:00
abstract::Vaccinia virus (VACV) was successfully used as a vaccine in the smallpox eradication campaign. Since then, it has been widely used in the development of vaccine and therapeutic vectors. However, methods of generating and purifying recombinant VACVs (rVACVs) are often time-consuming, cumbersome, and in some cases requi...
journal_title:Molecular therapy. Methods & clinical development
pub_type: 杂志文章
doi:10.1016/j.omtm.2020.03.026
更新日期:2020-03-30 00:00:00