Progress and prospects: immune responses to viral vectors

Nayak, Sushrusha; Herzog, Roland W.

doi:10.1038/gt.2009.148

Cited by 548 publications

(411 citation statements)

References 68 publications

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“…A key obstacle of stem cell-based gene therapy is the lack of safe and effective gene delivery systems. Viral vectors are the current gold standard for achieving high gene delivery efficiency into various human stem cells (27)(28)(29), but the broad clinical applications are limited by potential immune responses and unintended genomic integration events (21,22). Here, we report a safe and efficient method for transducing hADSCs with a full-length TRAIL using hydrolysable polymeric nanoparticles.…”

Section: Discussionmentioning

confidence: 99%

“…A recombinant soluble version of the transmembrane death ligand TRAIL has shown compelling preclinical results as a potential cancer therapeutic agent, but only rare clinical responses have been observed in clinical trials, possibly because of insufficient tumor exposure (17,18) and/or weak engagement of the extrinsic pathway (19,20). On the contrary, in the case of viralmediated TRAIL gene therapy, limitations arise from triggering immune responses and unintended genomic integration events (21,22), which remain a key bottleneck for broad clinical application.…”

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confidence: 99%

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Nanoparticle engineered TRAIL-overexpressing adipose-derived stem cells target and eradicate glioblastoma via intracranial delivery

Jiang

Fitch

Wang

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

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Glioblastoma multiforme (GBM) is one of the most intractable of human cancers, principally because of the highly infiltrative nature of these neoplasms. Tracking and eradicating infiltrating GBM cells and tumor microsatellites is of utmost importance for the treatment of this devastating disease, yet effective strategies remain elusive. Here we report polymeric nanoparticle-engineered human adipose-derived stem cells (hADSCs) overexpressing tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) as drug-delivery vehicles for targeting and eradicating GBM cells in vivo. Our results showed that polymeric nanoparticle-mediated transfection led to robust up-regulation of TRAIL in hADSCs, and that TRAIL-expressing hADSCs induced tumor-specific apoptosis. When transplanted in a mouse intracranial xenograft model of patient-derived glioblastoma cells, hADSCs exhibited long-range directional migration and infiltration toward GBM tumor. Importantly, TRAIL-overexpressing hADSCs inhibited GBM growth, extended survival, and reduced the occurrence of microsatellites. Repetitive injection of TRAIL-overexpressing hADSCs significantly prolonged animal survival compared with single injection of these cells. Taken together, our data suggest that nanoparticle-engineered TRAIL-expressing hADSCs exhibit the therapeutically relevant behavior of "seek-and-destroy" tumortropic migration and could be a promising therapeutic approach to improve the treatment outcomes of patients with malignant brain tumors.nanoparticle | adipose-derived stem cells | TRAIL | glioblastoma | tumor microsatellites

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Nanoparticle engineered TRAIL-overexpressing adipose-derived stem cells target and eradicate glioblastoma via intracranial delivery

Jiang

Fitch

Wang

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

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“…For the expression of a specific transgene in desired cells or tissues with the proper timing, many vectors carrying transgenes have been developed (Mátrai et al, 2010;Nayak & Herzog, 2010;Sliva & Schnierle, 2010). Retroviral, lentiviral, adenoviral, and adeno-associated viral vectors are used in various ways to achieve these goals.…”

Section: Introductionmentioning

confidence: 99%

Effective Transgene Constructs to Enhance Gene Therapy with Trichostatin A

Hayashi¹,

Ma²,

Kohno³

et al. 2011

Targets in Gene Therapy

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“…For example, approximately 40-69 % of healthy adults in America were found to be Ad5-seropositive by measuring the Ad5-neutralizing antibodies in blood samples (Nwanegbo et al, 2004). Systemic administration of adenovirus vectors also led to a rapid innate immune response against the capsid, vector DNA genome and viral protein (Yamaguchi et al, 2007;Nayak & Herzog, 2010), including induction of cytokines, inflammation, transient liver toxicity and thrombocytopenia. To avoid the neutralization of Ad5, or other immune responses, systemic administration could be replaced by local administration such as muscle injection, as muscle injection of Ad5 vector lowered the immune response.…”

Section: Discussionmentioning

confidence: 99%

Infecting mice with recombinant Ad5-BPI23-Fcγ1 virus protects against systemic Escherichia coli challenge

Kong

Chen

et al. 2012

Journal of Medical Microbiology

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Infections caused by Gram-negative bacteria (GNB) are increasingly common and can result in significant mortality rates due to the development of sepsis. To examine the potential usage of a recombinant Ad5-BPI 23 -Fcc1 virus as a biological treatment against systemic infection by GNB, a construct containing the human bactericidal/permeability increasing protein (BPI) gene, encoding the functional N terminus (amino acid residues 1-199) of human BPI, and the Fcc1 gene, encoding the Fc segment of human immunoglobulin G1, was inserted into an adenovirus serotype 5 (Ad5) chromosome to produce a recombinant Ad5-BPI 23 -Fcc1 virus. Human A549 cells in culture and BALB/c mice were infected with the recombinant Ad5-BPI 23 -Fcc1 virus and BPI 23 -Fcc1 expression was confirmed by Western blot analysis and ELISA. The concentrations of BPI 23 -Fcc1 protein were 5.59 mg ml "1 in vitro and 21.37 ng ml "1 in vivo and it was observed that these concentrations were sufficient to decrease endotoxin concentrations while enhancing bactericidal activity. In addition, mice treated with the recombinant Ad5-BPI 23 -Fcc1 virus had decreased levels of IL-1b and TNF-a and were protected from an E. coli O111 : B4 challenge. Our data support the concept that Ad5-mediated BPI 23 -Fcc1 gene delivery could be used as an ancillary biological treatment in the management of infection caused by GNB.

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Progress and prospects: immune responses to viral vectors

Cited by 548 publications

References 68 publications

Nanoparticle engineered TRAIL-overexpressing adipose-derived stem cells target and eradicate glioblastoma via intracranial delivery

Nanoparticle engineered TRAIL-overexpressing adipose-derived stem cells target and eradicate glioblastoma via intracranial delivery

Effective Transgene Constructs to Enhance Gene Therapy with Trichostatin A

Infecting mice with recombinant Ad5-BPI23-Fcγ1 virus protects against systemic Escherichia coli challenge

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