Gene transfer into human T lymphocytes and natural killer cells by Ad5/F35 chimeric adenoviral vectors

Schroers, Roland; Hildebrandt, York; Hasenkamp, Justin; Glaß, Bertram; Lieber, André; Wulf, Gerald; Piesche, Matthias

doi:10.1016/j.exphem.2004.03.010

Cited by 55 publications

(44 citation statements)

References 47 publications

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“…However, difficulties in genetically modifying primary NK cells have hampered further development in the field. Methods of transient genetic modification such as transfection, electroporation, nucleofection, and adenoviral infection are under constant development and have come a long way from applications on NK cell lines to GMP-compatible protocols for primary NK cells (Schroers et al, 2004;Zhang et al, 2004;Grund and Muise-Helmericks 2005;Goding et al, 2007;Schoenberg et al, 2008;Boissel et al, 2009). However, the possibility of stable genetic modification with transgenes enhancing or targeting NK cell cytotoxicity has many advantages.…”

Section: Discussionmentioning

confidence: 99%

Inhibition of Intracellular Antiviral Defense Mechanisms Augments Lentiviral Transduction of Human Natural Killer Cells: Implications for Gene Therapy

et al. 2012

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Section: Discussionmentioning

confidence: 99%

Inhibition of Intracellular Antiviral Defense Mechanisms Augments Lentiviral Transduction of Human Natural Killer Cells: Implications for Gene Therapy

et al. 2012

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“…Most investigators have demonstrated efficient gene transfer only in continuously growing NKcell lines [48][49][50][51][52][53][54] or reported methods yielding only transient gene expression. 37,55,56 We achieved stable expression of chimeric receptors in primary CD56 ϩ CD3 Ϫ NK cells by using an RD114-pseudotyped retroviral vector and specifically expanding primary CD56 ϩ CD3 Ϫ NK cells before they were exposed to the retrovirus, a step that allowed highly efficient gene expression. Although several cytokines such as IL-2, IL-12, and IL-15 stimulate NK cells, 27,57,58 their capacity to induce proliferation of resting CD56 ϩ CD3 Ϫ cells has been poor, unless accessory cells are present in the cultures.…”

Section: Discussionmentioning

confidence: 99%

Genetic modification of primary natural killer cells overcomes inhibitory signals and induces specific killing of leukemic cells

Imai

Iwamoto

Campana

2005

Blood

560

511

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IntroductionB-cell malignancies of children and adults, such as acute lymphoblastic leukemia (ALL), chronic lymphocytic leukemia (CLL), and non-Hodgkin lymphoma (NHL), are often incurable even with intensive chemotherapy. For many patients, bone marrow ablation followed by allogeneic hematopoietic stem cell transplantation is the only potentially curative option, but the disease may return after transplantation. 1 The well-documented association between T-cellmediated graft-versus-host disease (GvHD) and a delay or suppression of leukemic relapse after allogeneic stem cell transplantation 2-4 has led some investigators to manipulate GvHD by infusion of donor T lymphocytes. Although this procedure can induce a measurable antineoplastic response, [5][6][7][8] it carries the risk of severe GvHD, particularly in those patients (Ͼ 70%) who lack an HLA-identical donor. Moreover, in some B-cell malignancies, such as ALL, the effect of lymphocyte infusions is often inadequate. 6,9,10 Besides T lymphocytes, natural killer (NK) cells also exert cytotoxicity against cancer cells. 11 Recent studies have emphasized the potential of NK-cell therapy in recipients of allogeneic hematopoietic stem cell transplants. In animal models of transplantation, donor NK cells could lyse leukemic cells and host lymphohematopoietic cells without affecting nonhematopoietic tissues, 12 suggesting that NK-mediated graft-versus-leukemia responses may occur in the absence of systemic disease. Because NK cells are inhibited by self-HLA molecules, which bind to killer immunoglobulin-like receptors (KIRs), these findings have led to the clinical practice of selecting hematopoietic stem cell transplantation donors with an HLA and KIR type that favors NK-cell activation and thus could be expected to promote an antileukemic effect. [13][14][15] However, selection of the "best" donor is limited to patients who have more than one potential donor and the capacity of NK cells to lyse lymphoid cells is generally low and difficult to predict. 13,[15][16][17] Emerging evidence indicates that T lymphocytes genetically modified with chimeric receptors able to recognize a surface molecule of target cells and transduce activation signals can specifically enhance T-cell cytotoxicity against cancer cells both in vitro and in vivo. [18][19][20][21] The studies presented here are based on the concept that expression of chimeric receptors on NK cells could overcome HLA-mediated inhibitory signals, thus endowing the cells with cytotoxicity against otherwise NK-resistant cells. To test this hypothesis, we first developed a novel method that allows specific and vigorous expansion of NK cells lacking T-cell receptors (CD56 ϩ CD3 Ϫ cells) and their highly efficient transduction with chimeric receptors. Then, we tested the relative antileukemic effects of genetically modified NK cells bearing chimeric receptors (directed against CD19, a molecule widely expressed by malignant B cells) that deliver different primary and costimulatory signals. Materials and methods CellsThe C...

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“…The entry of Ad5 vectors can be rendered independent of CAR by modification of their fiber proteins. We and others have shown that Ad5 vectors containing fiber shaft and knob domains of human species B Ads very efficiently transduce a variety of human cells, including early hematopoietic progenitor cells [24][25][26][27], committed and malignant hematopoietic cells [28,29], and various primary cells of other tissues [30,31]. Likewise, hMSCs have been effectively transduced by Ad5 vectors carrying fiber domains of human Ad serotype 35 [32].…”

Section: For Reprints Contact: Reprints@alphamedpresscommentioning

confidence: 99%

Endowing Human Adenovirus Serotype 5 Vectors with Fiber Domains of Species B Greatly Enhances Gene Transfer into Human Mesenchymal Stem Cells

et al. 2005

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Bone marrow-derived human mesenchymal stem cells (hMSCs) lack the Coxsackie-adenovirus (Ad) receptor and thus are poorly transduced by vectors based on human Ad serotype 5 (Ad5). We investigated whether this problem could be overcome by using tropism-modified Ad5 vectors carrying fiber shaft domains and knobs of different human species B Ads (Ad5FBs). To allow quantitative analyses, these vectors coded for the enhanced green fluorescent protein (eGFP). Transgene expression analysis showed superior transduction of hMSCs by all Ad5FBs tested as compared with conventional Ad5 vectors. This was evident both by the frequency of eGFP-positive cells and by the eGFP level per cell. Highly efficient transduction of hMSCs, with limited variability between cells from different donors, was achieved with vectors displaying fiber domains of Ad serotypes 50, 35, and 16. These findings could not be reconciled with the very low levels of CD46, a recently identified receptor for species B Ads, on hMSCs, suggesting that AdFBs probably use receptors other than CD46 to enter these cells. We further observed that high eGFP levels were maintained in replication-restricted hMSCs for more than 30 days. In dividing hMSCs, foreign DNA delivered by Ad5FBs was expressed in a large fraction of the cells for approximately 3 weeks without compromising their replication capacity. Importantly, the transduced hMSCs retained their capacity to differentiate into adipocytes and osteoblasts when exposed to the appropriate stimuli.

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Gene transfer into human T lymphocytes and natural killer cells by Ad5/F35 chimeric adenoviral vectors

Cited by 55 publications

References 47 publications

Inhibition of Intracellular Antiviral Defense Mechanisms Augments Lentiviral Transduction of Human Natural Killer Cells: Implications for Gene Therapy

Inhibition of Intracellular Antiviral Defense Mechanisms Augments Lentiviral Transduction of Human Natural Killer Cells: Implications for Gene Therapy

Genetic modification of primary natural killer cells overcomes inhibitory signals and induces specific killing of leukemic cells

Endowing Human Adenovirus Serotype 5 Vectors with Fiber Domains of Species B Greatly Enhances Gene Transfer into Human Mesenchymal Stem Cells

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