Cationic Liposome Conjugation to Recombinant Adenoviral Vector Reduces Viral Antigenicity

Natsume, Atsushi; Mizuno, Masaaki; Ryuke, Yasushi; Yoshida, Jun

doi:10.1111/j.1349-7006.2000.tb00953.x

Cited by 26 publications

(12 citation statements)

References 17 publications

(20 reference statements)

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“…It is reported that mice subcutaneously injected with liposome-conjugated Ad vector showed a 6.5-fold reduction of anti-Ad antibodies with neutralizing activity, compared with those with unconjugated Ad vector. 43 In our study, however, the anti-adenovirus IgG levels from complex-injected mice were about 12-fold lower than those from Ad-hEndo injected alone. The PEG-PE cationic liposome system shows better protective activity from host immune clearance; this suggests that Ad-hEndo/Lipo can escape from host immunity and thus possibly be repeatedly applied through intravenous administration.…”

Section: Discussioncontrasting

confidence: 77%

Suppression of ovarian cancer growth via systemic administration with liposome-encapsulated adenovirus-encoding endostatin

Yang

Wang

et al. 2009

Cancer Gene Ther

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Gene therapy using adenoviral vector containing the endostatin gene is a promising strategy for advanced cancers. However, host immune response to adenovirus and the lack of the requisite coxsackie-adenovirus receptor (CAR) in many primary cells limit the in vivo application. Liposome-complexed adenoviral vectors have proven to be useful for enhancing gene delivery in target cells that lack adenoviral receptors and avoiding a neutralizing antibody response. Here, we investigated antitumor effects of intravenous administration with PEG-PE cationic liposome-encapsulated recombinant human endostatin adenovirus (Ad-hEndo) on CAR-negative ovarian cancer. Electron micrography (EM) showed that these liposomes efficiently encapsulated the vectors, allowing CAR-independent adenovector transduction. The results showed that the complex enhanced transfection efficiency of recombinant adenovirus. Prolonged systemic administration was performed in immunocompetent mice and did not induce significant antibody response. The antitumor effect with PEG-PE cationic liposome encapsulated with Ad-hE (Ad-hE/lipo) was evaluated in the human ovarian cancer model. Systemic administration was well tolerated and resulted in marked suppression of tumor growth in an established ovarian cancer model, which was associated with a decreased number of micro-vessels and increased apoptosis of tumor cells. Our study shows that PEG-PE cationic liposome-encapsulated Ad-hE (Ad-hE/Lipo) can be administrated intravenously and lastingly to inhibit angiogenesis, thus showing promising clinical application.

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Section: Discussioncontrasting

confidence: 77%

Suppression of ovarian cancer growth via systemic administration with liposome-encapsulated adenovirus-encoding endostatin

Yang

Wang

et al. 2009

Cancer Gene Ther

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“…Cells with nuclei harboring the human IFN-b (HuIFN-b) gene underwent unique morphologic changes characterized by bleb formation, cytoplasmic shrinkage, and DNA laddering, culminating in apoptotic cell death (data not shown). We also found that IFN-b gene transfer using cationic liposomes activated an immune response in the experimental glioma and surrounding tissues (Mizuno and Yoshida, 1998;Natsume et al, 1999Natsume et al, , 2000. On the basis of these experimental findings, we initiated clinical trials of this gene therapy.…”

Section: Introductionmentioning

confidence: 85%

“…In addition, growth of transplanted glioma (GL261) in immunocompetent mice (C57BL/6) was notably inhibited by intratumoral injection of the mouse IFN-b gene within cationic liposomes, and survival of treated mice was prolonged (Natsume et al, 1999). Immunologic responses arising in the brain were confirmed to be highly important, with the most potent immune cells being CD8 1 lymphocytes and macrophages (Natsume et al, 2000).…”

Section: Figmentioning

confidence: 95%

Human Gene Therapy for Malignant Gliomas (Glioblastoma Multiforme and Anaplastic Astrocytoma) by In Vivo Transduction with Human Interferon β Gene Using Cationic Liposomes

et al. 2004

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Transfer of interferon beta gene via cationic liposomes has been found to induce regression of experimental glioma. We performed a pilot clinical trial of safety and effectiveness of this interferon beta gene therapy in five patients with malignant glioma (glioblastoma multiforme or anaplastic astrocytoma). Transgene expression and antitumor activity were detected in four patients. Two patients showed a partial response (>50% tumor reduction) and two others had stable disease 10 weeks after beginning therapy. One patient could not be evaluated because of previous treatment with gamma-knife therapy. This study suggests the feasibility and safety of interferon beta gene therapy, which may become an important treatment option for patients with malignant glioma.

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“…1 Furthermore, we also found that Ad /SUV reduced antigenicity for Ad vector in vivo. 2 In this paper, we investigated whether Ad / SUV, compared to Ad vector alone, can induce a more effective antitumor activity against experimental (subcutaneous [s.c. ] and intracranial ) glioma models in mice.…”

mentioning

confidence: 99%

Cationic liposomes conjugation to recombinant adenoviral vectors containing herpes simplex virus thymidine kinase gene followed by ganciclovir treatment reduces viral antigenicity and maintains antitumor activity in mouse experimental glioma models

2002

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Gene therapy using adenoviral ( Ad ) vector containing herpes simplex virus thymidine kinase ( AxCAHSV -tk ) followed by the administration of ganciclovir ( GCV ) has been a promising therapy for cancer including malignant gliomas. However, there remain numerous problems to overcome, such as the high immunogenicity and toxicity of Ad vector. To optimize the therapy, we investigated whether a conjugation of our original cationic liposomes and Ad vectors reduces viral antigenicity and maintains the antitumor activity in mouse experimental ( subcutaneous and intracranial ) glioma models. Our original liposomes consist of N -(a -trimethylammonioacetyl ) -didodecyl -D -glutamate chloride, dilauroyl phosphatidylcholine, and dioleoyl phosphatidylethanolamine in a molar ratio of 1:2:2. AxCAHSV -tk and GCV showed a remarkable inhibition of experimental glioma growth. The growth -inhibitory effect decreased in mice previously immunized with another Ad vector ( AxCALacZ ). In contrast, the conjugation of AxCAHSV -tk and liposomes did not diminish the growth -inhibitory effect. Furthermore, the conjugation reduced antigenicity for Ad vector in vivo. These findings suggest that suicide gene therapy, using a conjugation of AxCAHSV -tk and our liposomes, is a feasible approach for human cancer gene therapy, especially malignant gliomas.

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Cationic Liposome Conjugation to Recombinant Adenoviral Vector Reduces Viral Antigenicity

Cited by 26 publications

References 17 publications

Suppression of ovarian cancer growth via systemic administration with liposome-encapsulated adenovirus-encoding endostatin

Suppression of ovarian cancer growth via systemic administration with liposome-encapsulated adenovirus-encoding endostatin

Human Gene Therapy for Malignant Gliomas (Glioblastoma Multiforme and Anaplastic Astrocytoma) by In Vivo Transduction with Human Interferon β Gene Using Cationic Liposomes

Cationic liposomes conjugation to recombinant adenoviral vectors containing herpes simplex virus thymidine kinase gene followed by ganciclovir treatment reduces viral antigenicity and maintains antitumor activity in mouse experimental glioma models

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