Patient monitoring and follow‐up in lentiviral clinical trials

McGarrity, Gerard J.; Hoyah, Gloria; Winemiller, April; Andre, Kris; Stein, David; Blick, Gary; Greenberg, Richard N.; Kinder, Clifford; Zolopa, Andrew; Binder-Scholl, Gwen; Tebas, Pablo; June, Carl H.; Humeau, Laurent; Rebello, Tessio

doi:10.1002/jgm.2691

Cited by 96 publications

(74 citation statements)

References 14 publications

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“…The integration sites of the vectors were mapped in CD4+ T cells, and no adverse events were reported. 131,132 These results confirmed the previously described HIV-1 integration profile and thus further backed up the safety profile of LVs. 131,133 Several Phase I gene therapy trials were performed with LV to modify CD34+ HSC.…”

Section: Vectors Based On Lentivirusessupporting

confidence: 85%

Improving miRNA Delivery by Optimizing miRNA Expression Cassettes in Diverse Virus Vectors

Herrera-Carrillo

Liu

Berkhout

2017

Human Gene Therapy Methods

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The RNA interference pathway is an evolutionary conserved post-transcriptional gene regulation mechanism that is exclusively triggered by double-stranded RNA inducers. RNAi-based methods and technologies have facilitated the discovery of many basic science findings and spurred the development of novel RNA therapeutics. Transient induction of RNAi via transfection of synthetic small interfering RNAs can trigger the selective knockdown of a target mRNA. For durable silencing of gene expression, either artificial short hairpin RNA or microRNA encoding transgene constructs were developed. These miRNAs are based on the molecules that induce the natural RNAi pathway in mammals and humans: the endogenously expressed miRNAs. Significant efforts focused on the construction and delivery of miRNA cassettes in order to solve basic biology questions or to design new therapy strategies. Several viral vectors have been developed, which are particularly useful for the delivery of miRNA expression cassettes to specific target cells. Each vector system has its own unique set of distinct properties. Thus, depending on the specific application, a particular vector may be most suitable. This field was previously reviewed for different viral vector systems, and now the recent progress in the field of miRNA-based gene-silencing approaches using lentiviral vectors is reported. The focus is on the unique properties and respective limitations of the available vector systems for miRNA delivery.Keywords: miRNA cassettes, gene therapy, viral vectors, vector tropism INTRODUCTION NON-CODING RNA MOLECULES play an essential role in gene regulation of the cell via a mechanism called RNA interference (RNAi). The RNAi mechanism is evolutionary conserved in eukaryotes and triggers the sequence-specific inhibition or degradation of a single or a unique set of complementary mRNAs. Three small RNA classes have been described to participate in mammalian RNAi mechanisms: microRNAs (miRNAs), 1,2 endogenous small interfering RNAs (endo-siRNAs), 3 and PIWI-associated RNAs (piRNAs). 4 The endo-siRNAs and piRNAs are involved in suppression of transposable elements. The miRNAs are broadly involved in the regulated expression of multiple cellular genes and execute their effect at the posttranscriptional level. 5,6 MiRNA-mediated regulation of gene expression plays a significant role in cell metabolism and cellular developmental and differentiation processes in mammals. More than a thousand human miRNAs have already been identified that are involved in the regulated expression of around 30% of all genes, which is a conservative estimate.7 Because of the miRNA abundance and their important regulatory functions, these molecules have received much attention from the scientific community over the last decade. For instance, efforts have been made to explain the biological function of the natural miRNAs by identifying the target mRNA and the role in cellular physiology. On the other hand, the design of man-made miRNA mimics to impose control over gene expression beca...

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Section: Vectors Based On Lentivirusessupporting

confidence: 85%

Improving miRNA Delivery by Optimizing miRNA Expression Cassettes in Diverse Virus Vectors

Herrera-Carrillo

Liu

Berkhout

2017

Human Gene Therapy Methods

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“…And even though no adverse events have been reported, there is less experience in clinical trials with gene-targeting methods than with lentivirusbased transduction. Thus, we opted for lentivirus-based gene engineering (39)(40)(41). Furthermore, we are the first to engage in miRNA technology for knocking down the HIV coreceptor CCR5 in CD4 ϩ T cells via gene engineering of CD34 ϩ cells.…”

Section: Discussionmentioning

confidence: 99%

Lentivector Knockdown of CCR5 in Hematopoietic Stem and Progenitor Cells Confers Functional and Persistent HIV-1 Resistance in Humanized Mice

Myburgh

Ivic

Pepper

et al. 2015

J Virol

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Gene-engineered CD34؉ hematopoietic stem and progenitor cells (HSPCs) can be used to generate an HIV-1-resistant immune system. However, a certain threshold of transduced HSPCs might be required for transplantation into mice for creating an HIVresistant immune system. In this study, we combined CCR5 knockdown by a highly efficient microRNA (miRNA) lentivector with pretransplantation selection of transduced HSPCs to obtain a rather pure population of gene engineered CD34

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“…with anti-CD3/anti-CD28 monoclonal antibodies coated beads; autologous antigen-presenting cells from donors; anti-CD3 antibodies in combination with feeder cells and growth factors, such as IL-2 [13,14].…”

mentioning

confidence: 99%

Use of Chimeric Antigen Receptor T Cells in Allogeneic Hematopoietic Stem Cell Transplantation

Zhang

Zhong

et al. 2018

Immunotherapy

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The chimeric antigen receptor T (CAR-T) cells play an antileukemia role, and can be used to treat or prevent relapse by targeting minimal residual disease for patients undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT). However, the infusion of allogeneic CAR-T cells may also cause graft-versus-host disease, which limited their applications during and after allo-HSCT. In this review, we discuss the clinical trials that applying CAR-T cells before allo-HSCT and the use of donor-derived CAR-T cells as conditioning regimen during allo-HSCT. At last, we analyzed the effect of donor-derived CAR-T cells on preventive infusion after allo-HSCT.

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Patient monitoring and follow‐up in lentiviral clinical trials

Abstract: Data from this small population suggest that there is no apparent risk for serious adverse events with the use of lentiviral vectors.

Cited by 96 publications

References 14 publications

Improving miRNA Delivery by Optimizing miRNA Expression Cassettes in Diverse Virus Vectors

Improving miRNA Delivery by Optimizing miRNA Expression Cassettes in Diverse Virus Vectors

Lentivector Knockdown of CCR5 in Hematopoietic Stem and Progenitor Cells Confers Functional and Persistent HIV-1 Resistance in Humanized Mice

Use of Chimeric Antigen Receptor T Cells in Allogeneic Hematopoietic Stem Cell Transplantation

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