Isolated limb perfusion: a novel delivery system for wild-type p53 and fiber-modified oncolytic adenoviruses to extremity sarcoma

Hannay, Jonathan; Davis, Joseph R.; Yu, Dihua; Liu, J.; Fang, Bingliang; Pollock, Raphael E.; Lev, Dina

doi:10.1038/sj.gt.3302911

Cited by 17 publications

(10 citation statements)

References 28 publications

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“…Intrathecal injection of adenovirus vector (Ad) expressing mouse Cx43 gene (Ad-Cx43) into naïve mice did not lead to significant tissue damage and gliosis in spinal dorsal horn compared with spinal dorsal horn from mice injected with saline (data not shown). Seven days after intrathecal injection of either Ad-Control (adenovirus without the Cx43 gene) or Ad-Cx43 in mice with a sham surgery, expression of hexon protein, a major coat protein of adenoviruses used as a marker of adenovirus infection (Hannay et al, 2007;Piao et al, 2009), was observed in the dorsal horn by immunofluorescence staining, indicating successful infection of cells in the spinal dorsal horn (Fig. 3A, and Suppl.…”

Section: Up-regulation Of Spinal Cord Cx43 By Recombinant Adenovirus mentioning

confidence: 96%

Tumor necrosis factor-mediated downregulation of spinal astrocytic connexin43 leads to increased glutamatergic neurotransmission and neuropathic pain in mice

Morioka

Zhang

Nakamura

et al. 2015

Brain, Behavior, and Immunity

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Section: Up-regulation Of Spinal Cord Cx43 By Recombinant Adenovirus mentioning

confidence: 96%

Tumor necrosis factor-mediated downregulation of spinal astrocytic connexin43 leads to increased glutamatergic neurotransmission and neuropathic pain in mice

Morioka

Zhang

Nakamura

et al. 2015

Brain, Behavior, and Immunity

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“…Further modifications of the retargeted adenovirus particles are the internal ligand incorpo- ration into the extended short-shafted fiber and the insertion of tandem copies of the peptide ligands. Fiber--modified p53 gene-bearing replication-selective adenoviruses (AdFLAGp53, Ad.hTC.GFP/E1a.RGD) entered xenografted human leiomyosarcoma cells in which the viruses replicated, inserted the wild p53 gene, and induced the upregulation of the cell cycle inhibitor p21 Cip1/Waf1 pathway [146]. Bypassing the CAR entry--site, mosaic fiber adenovirus serotype 5, containing reovirus sigma-1 and adenovirus serotype 3 knob, readily infected ovarian carcinoma cells [416].…”

Section: Adenovirusesmentioning

confidence: 99%

Natural and genetically engineered viral agents for oncolysis and gene therapy of human cancers

Sinkovics

Horváth

2008

Arch. Immunol. Ther. Exp.

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Based on personal acquaintances and experience dating back to the early 1950s, the senior author reviews the history of viral therapy of cancer. He points out the difficulties encountered in the treatment of human cancers, as opposed by the highly successful viral therapy of experimentally maintained tumors in laboratory animals, especially that of ascites carcinomas in mice. A detailed account of viral therapy of human tumors with naturally oncolytic viruses follows, emphasizing the first clinical trials with viral oncolysates. The discrepancy between the high success rates, culminating in cures, in the treatment of tumors of laboratory animals, and the moderate results, such as stabilizations of disease, partial responses, very rare complete remissions, and frequent relapses with virally treated human tumors is recognized. The preclinical laboratory testing against established human tumor cell lines that were maintained in tissue cultures for decades, and against human tumors extricated from their natural habitat and grown in xenografts, may not yield valid results predictive of the viral therapy applied against human tumors growing in their natural environment, the human host. Since the recent discovery of the oncosuppressive efficacy of bacteriophages, the colon could be regarded as the battlefield, where incipient tumor cells and bacteriophages vie for dominance. The inner environment of the colon will be the teaching ground providing new knowledge on the value of the anti-tumor efficacy of phage-induced innate anti-tumor immune reactions. Genetically engineered oncolytic viruses are reviewed next. The molecular biology of viral oncolysis is explained in details. Elaborate efforts are presented to elucidate how gene product proteins of oncolytic viruses switch off the oncogenic cascades of cancer cells. The facts strongly support the conclusion that viral therapy of human cancers will remain in the front lines of modern cancer therapeutics. It may be a combination of naturally oncolytic viruses and wild-type viruses rendered oncolytic and harmless by genetic engineering, that will induce complete remissions of human tumors. It may be necessary to co-administer certain chemotherapeutic agents, advanced cancer vaccines, or even immune lymphocytes, and targeted therapeuticals, to ascertain, that remissions induced by the viral agents will remain complete and durable; will co-operate with anti-tumor host immune reactions, and eventually will result in cures of advanced metastatic human cancers.

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“…We used a model of athymic rnu/rnu (nude) rats bearing human soft-tissue sarcoma xenografts (16). We show that targeted AAVP (i) allows ligand-directed targeting of human sarcoma xenografts in a preclinical setting; (ii) provides molecular imaging of reporters; (iii) is suitable for serial noninvasive monitoring of soft-tissue sarcoma; and, as a proof-of-concept, (iv) enables response prediction to a cytotoxic.…”

mentioning

confidence: 99%

A preclinical model for predicting drug response in soft-tissue sarcoma with targeted AAVP molecular imaging

Hajitou

Lev

Hannay

et al. 2008

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

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Human sarcomas are rare but diverse malignant tumors derived from mesenchymal tissue. Clinical response to therapy is currently determined by the modified World Health Organization (WHO) criteria or the Response Evaluation Criteria in Solid Tumors (RECIST), but these standards correlate poorly with sarcoma patient outcome. We introduced ligand-directed particles with elements of AAV and phage (AAVP) to enable integration of tumor targeting to molecular imaging. We report drug-response monitoring and prediction in a nude rat model of human sarcoma by AAVP imaging. As a proof-of-concept, we imaged Herpes simplex thymidine kinase in a clinic-ready setting with PET to show that one can a priori predict tumor response to a systemic cytotoxic. Given the target expression in patient-derived sarcomas, this platform may be translated in clinical applications. Sarcoma-specific ligands and promoters may ultimately lead to an imaging transcriptome.H uman sarcomas are rare yet heterogeneous malignant tumors from mesenchymal tissues (1). Monitoring drug responses in soft-tissue sarcoma has long been clinically problematic. Currently, responses are determined by the modified World Health Organization (WHO) criteria (2-4) or the Response Evaluation Criteria in Solid Tumors (RECIST) (5-7), which require marked tumor size decrease for patients to be considered responding to therapy. A major assumption of these criteria is that a solid tumor volume is directly proportional to the cancer cell number. However, in soft-tissue sarcomas, there are reasons to challenge such an assumption (8). First, in addition to tumor cells, sarcomas contain nonmalignant stromal cells and extracellular matrix (ECM) that do not disappear, even if the malignant component is treated. Moreover, when cytotoxics are used against sarcomas, there is often associated necrosis resulting in reduced total cell number but not necessarily overall tumor size changes. Finally, even if a soft-tissue sarcoma is predominantly or entirely composed of cancer cells, its remnant composition may not be fully eliminated when tumor cells are destroyed by therapy, because myxoid-type degeneration is not always promptly removed. Ultimately, the modified WHO criteria and RECIST correlate poorly with drug response and outcome in patients with soft-tissue sarcomas; validation in this setting is sporadic and restricted. In another level of complexity, drug responses in patients with soft-tissue sarcoma are determined through standard methods, such as CT, MRI, or PET scans. However, because systematic quantitative measurements have not been established because of the rarity and diversity of soft-tissue sarcomas, decreases in tumor size and/or density are not accepted as unequivocal evidence of response. Consequently, many conventional soft-tissue sarcoma responses in individual patients are evaluated qualitatively. Thus, new or alternative quantitative imaging criteria to improve management and follow-up of responses were proposed in ref. 9.We have introduced a hybrid vector that ena...

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Isolated limb perfusion: a novel delivery system for wild-type p53 and fiber-modified oncolytic adenoviruses to extremity sarcoma

Cited by 17 publications

References 28 publications

Tumor necrosis factor-mediated downregulation of spinal astrocytic connexin43 leads to increased glutamatergic neurotransmission and neuropathic pain in mice

Tumor necrosis factor-mediated downregulation of spinal astrocytic connexin43 leads to increased glutamatergic neurotransmission and neuropathic pain in mice

Natural and genetically engineered viral agents for oncolysis and gene therapy of human cancers

A preclinical model for predicting drug response in soft-tissue sarcoma with targeted AAVP molecular imaging

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