Cancer gene therapy with HSV‐
            <i>tk</i>
            /GCV system depends on t‐cell‐mediated immune responses and causes apoptotic death of tumor cells
            <i>In vivo</i>

Kuriyama, Shigeki; Kikukawa, Masaji; Masui, Kazuhiro; Okuda, Hiromichi; Nakatani, Toshiya; Akahane, Takemi; Mitoro, Akira; Tominaga, Kentaro; Tsujinoue, Hirohisa; Yoshiji, Hitoshi; Okamoto, Shingo; Fukui, Hiroshi; Ikenaka, Kazuhiro

doi:10.1002/(sici)1097-0215(19991029)83:3<374::aid-ijc13>3.0.co;2-#

Cited by 57 publications

(33 citation statements)

References 17 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…A vaccination effect has been suggested to be important for the effect of the two chemotherapy models cytosine deaminase/5-fluorocytosine (Consalvo et al, 1995;Kuriyama et al, 1999b;Morris, 1999;Pierrefite-Carle et al, 1999) and herpes simplex virus thymidine kinase/ganciclovir (Barba et al, 1994;Yamamoto et al, 1997;Kuriyama et al, 1999a), and for the effect of photodynamic therapy (PDT) (Chen et al, 1997;Chen et al, 1999). These modalities induce tumour cell necrosis, and an inflammatory microenvironment, which is critical for eliciting an efficient immune response (Melcher et al, 1998;Todryk et al, 1999;Sauter et al, 2000).…”

Section: Discussionmentioning

confidence: 99%

Resistance to tumour challenge after tumour laser thermotherapy is associated with a cellular immune response

et al. 2005

View full text Add to dashboard Cite

Previous studies in our laboratory have shown that interstitial laser thermotherapy (ILT) of an experimental liver tumour is superior to surgical excision, at least partly due to a laser-induced immunological effect. The aim of the present study was to investigate the time -response relationship of the ILT-induced immunisation and the cellular response of macrophages and lymphocytes. A dimethylhydrazine-induced adenocarcinoma was transplanted into the liver of syngeneic rats. Rats with tumour were treated 6 -8 days later (tumour size 0.25 -0.40 cm 3 ) with ILT of tumour or resection of the tumour-bearing lobe. Two groups of rats without tumour were treated with resection of a normal liver lobe or ILT of normal liver. A challenging tumour was implanted into the liver of each rat 2, 5 or 10 weeks after primary treatment. Rats were killed 6, 12 and 48 days (or earlier due to their condition) after challenge (n ¼ 8 in all groups). Immunohistochemical techniques were used to determine lymphocytes (CD8, CD4) and macrophages (ED1, ED2) in rats having had treatment of a primary tumour. Interstitial laser thermotherapy of the first tumour was followed by eradication of challenging tumour and absence of tumour spread. This contrasted with rapid growth and spread of challenging tumour in the other groups. In the challenging vital tumour tissue and in the interface between the tumour and surroundings, the number of ED1 macrophages and CD8 lymphocytes was higher in rats having been treated with the ILT of tumour than in those having undergone resection of the tumour-bearing lobe. The number of ED2 macrophages and CD4 lymphocytes was low and did not vary between these two groups. Interstitial laser thermotherapy elicited an immune response that eradicated a challenging tumour and was associated with increased numbers of tumour-infiltrating macrophages and CD8 lymphocytes.

show abstract

Section: Discussionmentioning

confidence: 99%

Resistance to tumour challenge after tumour laser thermotherapy is associated with a cellular immune response

et al. 2005

View full text Add to dashboard Cite

show abstract

“…By restricting HSVtk activity, it is possible to limit the potent bystander effect of ganciclovir activation, thereby enhancing this promising strategy in therapeutic areas where it has already shown efficacy, but with toxicity. For example, therapy of solid tumors, many of which have been successfully treated with HSVtk and ganciclovir 31,32 could be more optimally treated with the use of our anti-hexon antibody adenoviral vector delivery system. HSVtk with co-administration of ganciclovir has also been demonstrated to inhibit the development of experimental arterial restenosis effectively following angioplasty.…”

Section: Discussionmentioning

confidence: 99%

Localized adenovirus gene delivery using antiviral IgG complexation

et al. 2001

View full text Add to dashboard Cite

Gene therapy with viral vectors has progressed to clinical trials. However, the localization of viral vector delivery to diseased target sites remains a challenge. We tested the hypothesis that an adenoviral vector could be successfully delivered by complexation with a specific antibody that is bound to a biodegradable matrix designed for achieving localized gene transduction. We report the first successful delivery system based upon antibody immobilization of virions in a type I collagen-avidin gel using a polyclonal biotinylated IgG specific for the adenovirus hexon. In vitro stability studies demonstrated retention of viral vector activity with antibody-complexed adenovirus collagen gel preparations, in comparison to loss of vector activity from collagen gels prepared with nonspecific biotinylated IgG. Cell culture investigations using this antibody-controlled release system for adenoviral vector transduction of rat aortic smooth muscle cells (A10) demonstrated a significantly more localized reporter expression (␤-galactosidase) compared with non-antibody-complexed controls. Herpes simplex thymidine kinase (HSVtk) adenoviral vectors were immobilized on avidin-collagen gels via this antibody-com-

show abstract

“…In many tumor cell types, apoptosis is the prevalent response to GCV of both TK -bearing cells 2,12,18,28,51 and of bystander cells. 5,12,19 Nonapoptotic, e.g., necrotic, cell death was reported in some tumor cell types such as B16 melanoma after TK /GCV therapy.…”

mentioning

confidence: 99%

TRAIL enhances thymidine kinase/ganciclovir gene therapy of neuroblastoma cells

et al. 2002

View full text Add to dashboard Cite

The clinical benefit of suicide gene therapy of tumors has been marginal, mostly due to the low gene transfer efficiency in vivo. The death -inducing ligand, TRAIL, effectively kills many tumor cell types, while sparing most normal tissues. We hypothesized that TRAIL may enhance HSV thymidine kinase / ganciclovir ( TK / GCV ) gene therapy of tumor cells by augmenting both target and bystander cell kill. Human SH -EP neuroblastoma cells expressing TK as well as bystander cells were effectively killed by apoptosis, and their clonogenicity was ablated following GCV. Human TRAIL enhanced TK / GCV -induced cell death and decreased clonogenicity of TK -expressing cells and also of bystander cells. Cooperation between TRAIL and TK / GCV depended both on caspase activation and on mitochondrial apoptogenic function because both the broad -spectrum caspase inhibitor zVAD.fmk and overexpression of Bcl -2 decreased enhancement of cell kill by TRAIL. Facilitation of TRAIL signalling by up -regulation of TRAIL receptors did not contribute to enhancement because cell surface expression of the agonistic TRAIL receptors 1 and 2 was not increased by TK / GCV. In conclusion, the concerted activation of caspases and the mitochondrial amplification of caspase activation by TK / GCV may explain the cooperative effect of TK / GCV and TRAIL on the kill of neuroblastoma cells. Because combined treatment also augmented the bystander cell kill, the addition of TRAIL may increase the efficacy of TK / GCV gene therapy of neuroblastoma.

show abstract

Cancer gene therapy with HSV‐ tk /GCV system depends on t‐cell‐mediated immune responses and causes apoptotic death of tumor cells In vivo

Cited by 57 publications

References 17 publications

Resistance to tumour challenge after tumour laser thermotherapy is associated with a cellular immune response

Resistance to tumour challenge after tumour laser thermotherapy is associated with a cellular immune response

Localized adenovirus gene delivery using antiviral IgG complexation

TRAIL enhances thymidine kinase/ganciclovir gene therapy of neuroblastoma cells

Contact Info

Product

Resources

About