Readministration of helper-dependent adenovirus to mouse lung

Koehler, David R.; Martin, Bernard; Corey, Mary; Palmer, D. Jason; Ng, Phillip; Tanswell, A. Keith; Hu, Jim

doi:10.1038/sj.gt.3302712

Cited by 52 publications

(53 citation statements)

References 47 publications

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“…However, Koehler et al 54 have recently demonstrated that simple readministration of HDAd of the same serotype, but not FGAd, can lead to successful pulmonary transduction. In this study, a second administration of HDAd to the mouse lung was possible with minimal loss of transgene expression.…”

Section: Prospectsmentioning

confidence: 99%

Progress and prospects: gene therapy for genetic diseases with helper-dependent adenoviral vectors

Brunetti‐Pierri

2008

Gene Ther

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Preclinical studies in small and large animal models using helper-dependent adenoviral vectors (HDAds) have generated promising results for the treatment of genetic diseases. However, clinical translation is complicated by the dosedependent, capsid-mediated acute toxic response following systemic vector injection. With the advancements in vectorology, a better understanding of vector-mediated toxicity, and improved delivery methods, HDAds may emerge as an important vector for gene therapy of genetic diseases and this report highlights recent progress and prospects in this field.

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Section: Prospectsmentioning

confidence: 99%

Progress and prospects: gene therapy for genetic diseases with helper-dependent adenoviral vectors

Brunetti‐Pierri

2008

Gene Ther

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“…In that sense efforts have been focused on the reduction of the immunogenic response by removing nearly the complete viral genome coding sequences. The latter acquired the name "gutless adenovirus" and requires the help of a helper virus in order to produce viral particles (Koehler et al, 2005;Koehler et al, 2006). Although deficient in the ability of replication as standalone vector, it maintains high infectivity rates and wide tropism.…”

Section: Adenovirusesmentioning

confidence: 99%

Anticancer Gene Transfer for Cancer Gene Therapy

Pazarentzos

Mazarakis

2014

Advances in Experimental Medicine and Biology

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Gene therapy vectors are among the treatments currently used to treat malignant tumors. Gene therapy vectors use a specific therapeutic transgene that causes death in cancer cells. In early attempts at gene therapy, therapeutic transgenes were driven by nonspecific vectors which induced toxicity to normal cells in addition to the cancer cells. Recently, novel cancer specific viral vectors have been developed that target cancer cells leaving normal cells unharmed. Here we review such cancer specific gene therapy systems currently used in the treatment of cancer and discuss the major challenges and future directions in this field.

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“…However, other studies have shown that with readministration of HD-Ad vector particles, there is a decrease in transgene expression correlating with an increasing Ab titer against the virus, indicating that there may be an adaptive response being mounted against HD-Ad particles (9). Nevertheless, none of the studies to date have assessed the ability of HD-Ad particles to induce T cell immune response upon airway delivery (9,10). Among gene therapy vectors, adeno-associated virus (AAV)-derived vectors are thought to be the least immunogenic (11).…”

Section: Characterization Of Pulmonary T Cell Response Tomentioning

confidence: 99%

“…The first dose being 1 ϫ 10 11 vector particles/mouse as a high dose, which has been shown to result in therapeutic effects in CFTR knockout mice (19). The second dose was a low dose of 5 ϫ 10 9 vector particles/mouse and is 3-fold lower than the low dose normally used for HD-Ad pulmonary delivery (9,19). At first, we looked at the infiltration of T cells in the BALF of mice at different time points after vector delivery.…”

Section: Hd-ad Vectors Induce T Cell Response Upon Pulmonary Deliverymentioning

confidence: 99%

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Characterization of Pulmonary T Cell Response to Helper-Dependent Adenoviral Vectors following Intranasal Delivery

Kushwah

Cao

2008

The Journal of Immunology

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In spite of the extensive research in the field of gene therapy, host immune responses continue to be the major barrier in translating basic research to clinical practice. Helper-dependent adenoviral (HD-Ad) vectors show great potential for pulmonary gene therapy, but the knowledge of pulmonary immune responses toward these vectors is very limited. In this study, we show that HD-Ad vectors are potent stimulators of dendritic cell (DC) maturation, thus leading to stimulation of T cell proliferation with ∼6% of naive CD4+ T cells from pulmonary mediastinal lymph node responding to HD-Ad-treated DCs. In contrast to the belief that HD-Ad vectors are unable to prime adaptive immune response, we show for the first time, through in vivo pulmonary studies in mice, that HD-Ad vectors can prime CD4+ and CD8+ T cell responses in the lung at high and substantially low doses. This indicates cross-presentation of HD-Ad-derived epitopes by DCs to prime CD8+ T cell responses. To assess the basis of pulmonary T cell response against HD-Ad vectors, we examined the response of conventional DCs (cDCs) and plasmacytoid DCs (pDCs) in the lung. In response to HD-Ad delivery, there is induction of maturation in both cDC and pDC subsets, but it is the cDCs, not pDCs, that migrate rapidly to draining lymph nodes within the first 2 days after vector delivery to prime adaptive immune response against these vectors. These findings have implications for development of strategies to prevent adaptive immune responses against gene therapy vectors.

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Readministration of helper-dependent adenovirus to mouse lung

Cited by 52 publications

References 47 publications

Progress and prospects: gene therapy for genetic diseases with helper-dependent adenoviral vectors

Progress and prospects: gene therapy for genetic diseases with helper-dependent adenoviral vectors

Anticancer Gene Transfer for Cancer Gene Therapy

Characterization of Pulmonary T Cell Response to Helper-Dependent Adenoviral Vectors following Intranasal Delivery

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