PEGylated adenovirus vectors containing RGD peptides on the tip of PEG show high transduction efficiency and antibody evasion ability

Eto, Yusuke; Sekiguchi, Fumiko; Kurachi, Shinnosuke; Katayama, Kazufumi; Maeda, Mitsuko; Kawasaki, Koichi; Mizuguchi, Hiroyuki; Hayakawa, Tetsuo; Tsutsumi, Yasuo; Mayumi, Tadanori; Nakagawa, Shinsaku

doi:10.1002/jgm.699

Cited by 95 publications

(84 citation statements)

References 38 publications

(44 reference statements)

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“…A rational combination of both viral and nonviral vector components, thus, has promise to overcome the limitations of viral vector-mediated transfection. This may be achieved by viral surface coating with lipid (Gregory et APPROACHES FOR IMPROVING ISLET TRANSPLANTATION al., 2003); administration of viruses in liposomes (Ohmori et al, 2005); or Adv surface conjugation of ligands, spacers (Eto et al, 2005), and polymers (Fisher et al, 2001).…”

Section: ϫ5mentioning

confidence: 99%

“…PEGylation of Adv has been shown to protect the vectors from pre-existing and adaptive immune responses by reducing their interactions with immune cells (O'Riordan et al, 1999;Croyle et al, 2002;Eto et al, 2005;Mok et al, 2005). Mok et al (2005) studied PEG-modified first-generation and gutless Adv vectors for their transfection efficiency and immunogenicity in vitro and in vivo.…”

Section: ϫ5mentioning

confidence: 99%

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Biological and Biomaterial Approaches for Improved Islet Transplantation

2006

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Section: ϫ5mentioning

confidence: 99%

Section: ϫ5mentioning

confidence: 99%

Biological and Biomaterial Approaches for Improved Islet Transplantation

2006

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“…17,18) In addition, we and others have reported that PEG-Ad can evade pre-existing neutralizing anti-Adv Abs, thereby making repeated vector delivery to liver and lung feasible. 10,[19][20][21] ing the efficacy of PEG-Ad in reducing the production of neutralizing anti-Adv Abs. Although some reports show that mucosal administration of PEG-Ad reduces the production of neutralizing anti-Adv Abs, 10,22) no study has been carried out to examine the production of neutralizing anti-Adv Abs after systemic administration of PEG-Ad.…”

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confidence: 99%

Optimized PEGylated Adenovirus Vector Reduces the Anti-vector Humoral Immune Response against Adenovirus and Induces a Therapeutic Effect against Metastatic Lung Cancer

Eto

Yoshioka

Ishida

et al. 2010

Biological & Pharmaceutical Bulletin

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The use of gene transduction by viral vectors in human gene therapy is currently attracting a great deal of attention. In cancer therapy, gene therapy is expected to play a key role in next-generation treatments, as well as in complementing conventional treatment modalities, such as surgery, chemotherapy, and radiotherapy.1,2) Adenovirus vectors (Adv) have been very useful in clinical gene therapy because of their ability to propagate to a high titer and efficiently transduce cells and tissues regardless of the mitotic status of the cells. 3,4) Intratumoral injection of Adv has demonstrated therapeutic efficacy against primary tumors in several clinical trials. 5,6) However, the clinical application of Adv has been limited by several problems. The systemic administration of Adv can lead to the acute accumulation of Adv and transgene expression in the liver, which may cause marked hepatotoxicity and activate the acquired immune response. 4,7)Since systemic administration is required to treat distant metastases, it is currently difficult to use Adv to treat metastatic tumors, which are the major cause of mortality from cancer. Furthermore, because neutralizing antibodies (Abs) to Adv are highly prevalent in the human population, administration of high doses of Adv, which are needed to obtain sufficient therapeutic effects, causes negative side-effects. 8,9) In addition, neutralizing anti-Adv Abs are produced after administration of Adv in animal models.10,11) These preexisting or Adv-induced Abs can adversely affect the therapeutic effect of the Adv by attenuating the level of transgene expression.Covalent conjugation of polyethleneglycol (PEG) to the Adv surface, by a process called "PEGylation," is the one of the promising strategies to overcome these limitations. 4,12,13) Because of the steric hindrance of the PEG molecule, PEGylation can prolong the plasma half-life of molecules, prevent hepatic uptake, and alter the tissue distribution of the conjugates compared with the native form.14,15) The extended circulating lifetime in the blood induces the "enhanced permeability and retention" (EPR) effect, which is due to the leaky nature of tumor blood vessels. This effect results in increased delivery of the conjugates to tumor tissue. 16) We have examined the in vitro and in vivo characteristics of PEGylated Adv (PEG-Ad) manufactured using PEG of various molecular weights, and with various PEG modification rates. 17,18) With optimized modification conditions, PEG-Ad showed higher accumulation rates and transgene expression in tumors than unmodified Adv after systemic administration, due to the EPR effect.17,18) Furthermore, we showed that PEG-Ad encoding a therapeutic gene produced both stronger tumor-suppressive activity and fewer hepatotoxic side effects than unmodified Adv, suggesting that systemic administration of PEG-Ad has great potential for systemic cancer gene therapy. 17,18) In addition, we and others have reported that PEG-Ad can evade pre-existing neutralizing anti-Adv Abs, thereby making repeated vec...

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“…This resulted in a significant improvement in transduction and specificity of gene delivery into endothelial cells. These events have implications on the treatment of rheumatoid arthritis, inflammatory bowel disease and epithelial tumors (Eto et al, 2005;Ogawara et al, 2006). Transduction of bone marrow derived human mesenchymal stem cells (MSC) can be significantly improved by using a PEGylated AdV conjugated with a blocked poly-L-lysine.…”

Section: Chemical Modification Of the Adv Capsidmentioning

confidence: 99%