Regression of established macroscopic liver metastases after in situ transduction of a suicide gene.

Caruso, Manuel; Panís, Yves; Gagandeep, Singh; Houssin, D; Salzmann, Jean-Loup; Klatzmann, David

doi:10.1073/pnas.90.15.7024

Cited by 347 publications

(173 citation statements)

References 18 publications

Supporting

Mentioning

167

Contrasting

Unclassified

Order By: Relevance

“…This agrees with findings in studies in which antitumour immunity has been induced and where these two cell types have been found to be of importance (Caruso et al, 1993;Barba et al, 1994;Consalvo et al, 1995;Yamamoto et al, 1997;Xiang et al, 1998;Kuriyama et al, 1999a, b). Antitumour immunity is a complex phenomenon.…”

Section: Discussionsupporting

confidence: 89%

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: Discussionsupporting

confidence: 89%

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

“…Even 22 weeks after the end of the treatment, no tumor recurrence was detectable. Although some studies showed that at the doses needed to eliminate the tumor, GCV causes leukopenia, diarrhea, 508 and some treatment-related mortality, 51 in our experiments GCV treatment did not cause such symptoms in the animals. Also, we did not observe weight loss during GCV therapy.…”

Section: Discussioncontrasting

confidence: 67%

MIA (melanoma inhibitory activity) promoter mediated tissue-specific suicide gene therapy of malignant melanoma

Schoensiegel

Paschen

Sieger³

et al. 2004

Cancer Gene Ther

View full text Add to dashboard Cite

Suicide gene therapy of malignant melanoma essentially requires efficient gene transfer and highly selective therapeutic gene expression. To achieve this, recombinant adeno-associated virus (rAAV) particles were constructed containing the tissue-specific promoter of the human melanoma inhibitory activity (hMIA) gene combined with four copies of the enhancer element of the murine tyrosinase gene. Three melanoma and one cervix carcinoma cell line were infected with rAAV particles carrying a reporter gene under control of the enhancer/hMIA promoter in order to determine transcriptional activity and specificity of this system. Viral particles containing the enhancer/hMIA promoter mediated reporter gene activity only in melanoma cells, whereas infection with a cytomegalovirus (CMV)-based promoter construct induced unspecific gene expression. Correspondingly, transient transduction with viral particles bearing the HSVtk gene under the control of the enhancer/MIA promoter elements followed by treatment with ganciclovir (GCV) resulted in growth inhibition only in melanoma cells, whereas the CMV promoter-based construct induced unspecific cytotoxicity. In vivo experiments in nude mice demonstrated that tumors originating from human melanoma cells disappeared after stable, but not transient transduction with vectors bearing the HSVtk gene under the control of the enhancer/hMIA promoter in response to GCV application. In face of higher transduction efficiency, these rAAV particles might therefore be a useful tool for suicide gene therapy of malignant melanoma.

show abstract

“…21 Several studies have suggested the contribution of immunologic mechanisms in mediating the bystanderkilling effects in colon cancer cells. 22,23 We hypothesized that the bystander effect could be enhanced by inducing immunogenicity against the tumor. The GM-CSF gene was used because it is known to encode for a cytokine that is highly potent in inducing antitumor immunity.…”

Section: Discussionmentioning

confidence: 99%

Herpes simplex virus thymidine kinase and granulocyte macrophage colony-stimulating factor combination gene therapy in a murine CT26 cell colon cancer model

et al. 2004

View full text Add to dashboard Cite

We evaluated the antitumor effects of combination gene therapy on CT26 mouse colon cancer cells, using the genes for herpes simplex virus thymidine kinase gene HSV-TK combined with granulocyte macrophage colony-stimulating factor (GM-CSF) compared with HSV-TK alone. Cells, unmodified or retrovirally transduced with HSV-TK or GM-CSF, were inoculated subcutaneously into syngeneic BALB/c mice in various combinations. HSV-TK and GM-CSF were also delivered using different routes (in separate cells vs doubly transfected single cells). Both HSV-TK (with i.p. ganciclovir -GCV -treatment) and GM-CSF genes had independent antitumor effects, and given together they caused significant reduction in tumor volumes compared with the HSV-TK gene alone (Po0.001). Following GCV treatment, however, the treated/control ratios for tumor volumes were not different between tumors containing either HSV-TK alone or both genes (0.27 vs 0.25, respectively). Thus, the presence of GM-CSF did not increase the bystander effect of HSV-TK. Tumors receiving genes transferred in separate cells tended to be more consistently suppressed after GCV treatment than when both genes were transferred in the same cells, although this was not statistically significant. Thus, combination GM-CSF and HSV-TK gene therapy produced greater therapeutic efficacy than HSV-TK alone, but the bystander effect was not enhanced by GM-CSF.

show abstract

Regression of established macroscopic liver metastases after in situ transduction of a suicide gene.

Cited by 347 publications

References 18 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

MIA (melanoma inhibitory activity) promoter mediated tissue-specific suicide gene therapy of malignant melanoma

Herpes simplex virus thymidine kinase and granulocyte macrophage colony-stimulating factor combination gene therapy in a murine CT26 cell colon cancer model

Contact Info

Product

Resources

About