Efficient antitumor effects of carrier cells loaded with a fiber-substituted conditionally replicating adenovirus on CAR-negative tumor cells

Iguchi, Kazuo; Sakurai, Fuminori; Tomita, Kyoko; Katayama, Kazufumi; Yamaguchi, Tomoko; Kono, Kenji; Tagawa, Masatoshi; Kawabata, Masato; Shirakawa, Toshiro; Mizuguchi, Hiroyuki

doi:10.1038/cgt.2011.74

Cited by 12 publications

(8 citation statements)

References 39 publications

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“…Ad serotype group B viruses (e.g. Ad 5/35 virus and Ad 5/3) infect CAR-negative cell lines more efficiently than the Ad5 vector [ 14 ]. Moreover, recent studies utilizing B-subgroup adenovirus genotyped with adenovirus type 3 [ 15 ], type 11 [ 4 , 16 ] and type 35 [ 5 , 17 ] demonstrated significant anti-GBM effects.…”

Section: Introductionmentioning

confidence: 99%

Tamoxifen improves cytopathic effect of oncolytic adenovirus in primary glioblastoma cells mediated through autophagy

et al. 2015

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Oncolytic gene therapy using viral vectors may provide an attractive therapeutic option for malignant gliomas. These viral vectors are designed in a way to selectively target tumor cells and spare healthy cells. To determine the translational impact, it is imperative to assess the factors that interfere with the anti-glioma effects of the oncolytic adenoviral vectors. In the current study, we evaluated the efficacy of survivin-driven oncolytic adenoviruses pseudotyping with adenoviral fiber knob belonging to the adenoviral serotype 3, 11 and 35 in their ability to kill glioblastoma (GBM) cells selectively without affecting normal cells. Our results indicate that all recombinant vectors used in the study can effectively target GBM in vitro with high specificity, especially the 3 knob-modified vector. Using intracranial U87 and U251 GBM xenograft models we have also demonstrated that treatment with Conditionally Replicative Adenovirus (CRAd-S-5/3) vectors can effectively regress tumor. However, in several patient-derived GBM cell lines, cells exhibited resistance to the CRAd infection as evident from the diminishing effects of autophagy. To improve therapeutic response, tumor cells were pretreated with tamoxifen. Our preliminary data suggest that tamoxifen sensitizes glioblastoma cells towards oncolytic treatment with CRAd-S-5/3, which may prove useful for GBM in future experimental therapy.

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Section: Introductionmentioning

confidence: 99%

Tamoxifen improves cytopathic effect of oncolytic adenovirus in primary glioblastoma cells mediated through autophagy

et al. 2015

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“…Briefly, the immune system is by passed by viruses that are camouflaged under a different capsid or shielded with chemical compounds like polyethylene glycol in order to "trick" the immune system and be deliver to the tumor site. Stem cells, cancer stem cells, endothelial cells and progenitors, immune cells and even cancer cells as carriers have been, or are being tested for their efficacy and proof of principle (Iguchi et al, 2012;Hamada et al, 2007;Stoff-Khalili et al, 2007). Another approach to overcome the pre-existing immunity is the temporal immunosuppression using pharmacologic interference to bypass the adaptive and innate immune response.…”

Section: Hurdles For the Use Of Viruses As Delivery Vectorsmentioning

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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“…Tumors expressing CAR at a low level are thereby resistant to type 5 Ad-mediated gene transduction. A recent study showed that CD46 expression was not downregulated on mesothelioma cells [37], and recombinant type 5 Ad which replaced the fiber-knob region with that of type 35 Ad, shifting the Ad receptors from CAR to CD46 molecules, dramatically improved the infectivity [38]. Furthermore such a switching receptor-binding site may hinder the rapid production of neutralizing antibody since humans are less frequently exposed to type 35 Ad and many persons have not yet primed for the type 35 viral antigens.…”

Section: Optimizing Viruses-mediated Gene Therapymentioning

confidence: 99%

A Potential Therapeutic Strategy for Malignant Mesothelioma with Gene Medicine

Tada

Shimada

Hiroshima

et al. 2013

BioMed Research International

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Malignant mesothelioma, closely linked with occupational asbestos exposure, is relatively rare in the frequency, but the patient numbers are going to increase in the next few decades all over the world. The current treatment modalities are not effective in terms of the overall survival and the quality of life. Mesothelioma mainly develops in the thoracic cavity and infrequently metastasizes to extrapleural organs. A local treatment can thereby be beneficial to the patients, and gene therapy with an intrapleural administration of vectors is one of the potential therapeutics. Preclinical studies demonstrated the efficacy of gene medicine for mesothelioma, and clinical trials with adenovirus vectors showed the safety of an intrapleural injection and a possible involvement of antitumor immune responses. Nevertheless, low transduction efficiency remains the main hurdle that hinders further clinical applications. Moreover, rapid generation of antivector antibody also inhibits transgene expressions. In this paper, we review the current status of preclinical and clinical gene therapy for malignant mesothelioma and discuss potential clinical directions of gene medicine in terms of a combinatory use with anticancer agents and with immunotherapy.

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Efficient antitumor effects of carrier cells loaded with a fiber-substituted conditionally replicating adenovirus on CAR-negative tumor cells

Cited by 12 publications

References 39 publications

Tamoxifen improves cytopathic effect of oncolytic adenovirus in primary glioblastoma cells mediated through autophagy

Tamoxifen improves cytopathic effect of oncolytic adenovirus in primary glioblastoma cells mediated through autophagy

Anticancer Gene Transfer for Cancer Gene Therapy

A Potential Therapeutic Strategy for Malignant Mesothelioma with Gene Medicine

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