Preclinical study of an ex vivo gene therapy protocol for hepatocarcinoma

Lortal, Barbara; Gross, Fabian; Péron, Jean‐Marie; Pénary, Marie; Berg, D; Hennebelle, Isabelle; Favre, Gilles; Couderc, Bettina

doi:10.1038/cgt.2008.88

Cited by 5 publications

(3 citation statements)

References 43 publications

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“…Human MSC were isolated from the bone marrow of a healthy donor according to an already published protocol 19. Human primary fibroblast culture was established in the laboratory from a skin biopsy as previously described 20. These MSC and fibroblasts were immortalized using T antigen of the SV40 virus (pBABE largeT SV40, Addgene, USA).…”

Section: Methodsmentioning

confidence: 99%

Hospicells (ascites‐derived stromal cells) promote tumorigenicity and angiogenesis

Pasquet

Golzio

Mery-Lamarche

et al. 2009

Intl Journal of Cancer

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The microenvironment is known to play a dominant role in cancer progression. Cells closely associated with tumoral cells, named hospicells, have been recently isolated from the ascites of ovarian cancer patients. Whilst these cells present no specific markers from known cell lineages, they do share some homology with bone marrow‐derived or adipose tissue‐derived human mesenchymal stem cells (CD9, CD10, CD29, CD146, CD166, HLA‐1). We studied the role of hospicells in ovarian carcinoma progression. In vitro, these cells had no effect on the growth of human ovarian carcinoma cell lines OVCAR‐3, SKOV‐1 and IGROV‐1. In vivo, their co‐injection with adenocarcinoma cells enhanced tumor growth whatever the tumor model used (subcutaneous and intraperitoneally established xenografts in athymic mice). In addition, their injection increased the development of ascites in tumor‐bearing mice. Fluorescent macroscopy revealed an association between hospicells and ovarian adenocarcinoma cells within the tumor mass. Tumors obtained by coinjection of hospicells and human ovarian adenocarcinoma cells presented an increased microvascularization indicating that the hospicells could promote tumorigenicity of ovarian tumor cells in vivovia their action on angiogenesis. This effect on angiogenesis could be attributed to the increased HIF1α and VEGF expression associated with the presence of the hospicells. Collectively, these data indicate a role for these ascite‐derived stromal cells in promoting tumor growth by increasing angiogenesis.

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Section: Methodsmentioning

confidence: 99%

Hospicells (ascites‐derived stromal cells) promote tumorigenicity and angiogenesis

Pasquet

Golzio

Mery-Lamarche

et al. 2009

Intl Journal of Cancer

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“…The more classical is the non-specific immunotherapy aiming to administrate cytokines with antitumor effect (interferons, interleukins, etc.). To overcome some side effects provided by systemic administration gene therapy strategies has been developed to induce local interleukin or cytokine either by the tumor cells themselves or via ex-vivo approach (example of human fibroblast transduced with interleukin-12) [38,83,84,85,86,87,88]. Pre-clinical experiments have been conducted in vitro and in vivo aiming to produced interleukins (IL-2, IL-4, IL-6, IL-27, IL-1β, IL-24) and cytokines (GM-CSF, IFNα and β, TNFα).…”

Section: Therapeutic Genes and Pre-clinical Strategiesmentioning

confidence: 99%

Gene Therapy for Pancreatic Cancer: Specificity, Issues and Hopes

Rouanet

Lebrin²,

Gross³

et al. 2017

IJMS

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A recent death projection has placed pancreatic ductal adenocarcinoma as the second cause of death by cancer in 2030. The prognosis for pancreatic cancer is very poor and there is a great need for new treatments that can change this poor outcome. Developments of therapeutic innovations in combination with conventional chemotherapy are needed urgently. Among innovative treatments the gene therapy offers a promising avenue. The present review gives an overview of the general strategy of gene therapy as well as the limitations and stakes of the different experimental in vivo models, expression vectors (synthetic and viral), molecular tools (interference RNA, genome editing) and therapeutic genes (tumor suppressor genes, antiangiogenic and pro-apoptotic genes, suicide genes). The latest developments in pancreatic carcinoma gene therapy are described including gene-based tumor cell sensitization to chemotherapy, vaccination and adoptive immunotherapy (chimeric antigen receptor T-cells strategy). Nowadays, there is a specific development of oncolytic virus therapies including oncolytic adenoviruses, herpes virus, parvovirus or reovirus. A summary of all published and on-going phase-1 trials is given. Most of them associate gene therapy and chemotherapy or radiochemotherapy. The first results are encouraging for most of the trials but remain to be confirmed in phase 2 trials.

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“…For autologous-derived cell transplantations, fibroblasts have shown promise in a variety of tissues, including bone, neural, cardiac, and skeletal muscle. 8 Importantly, dermal fibroblasts (dFbs) are readily accessible in patients, expandable in vitro after a minimally invasive dermal biopsy, 9 and possess increased mitotic activity and resistance to differentiation into myofibroblasts compared with fibroblasts from other tissues. 10 …”

Section: Introductionmentioning

confidence: 99%

Engraftment potential of dermal fibroblasts following in vivo myogenic conversion in immunocompetent dystrophic skeletal muscle

Muir

Nguyen

Hauschka

et al. 2014

Molecular Therapy - Methods & Clinical Development

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Autologous dermal fibroblasts are promising candidates for enhancing muscle regeneration in Duchenne muscular dystrophy (DMD) due to their ease of isolation, immunological compatibility, and greater proliferative potential than DMD satellite cells. We previously showed that mouse fibroblasts, after MyoD-mediated myogenic reprogramming in vivo, engraft in skeletal muscle and supply dystrophin. Assessing the therapeutic utility of this system requires optimization of conversion and transplantation conditions and quantitation of engraftment so that these parameters can be correlated with possible functional improvements. Here we derived dermal fibroblasts from transgenic mice carrying mini-dystrophin, transduced them by lentivirus carrying tamoxifen-inducible MyoD, and characterized their myogenic and engraftment potential. After cell transplantation into muscles of immunocompetent dystrophic mdx4cv mice, tamoxifen treatment drove myogenic conversion and fusion into myofibers that expressed high levels of mini-dystrophin. Injecting 50,000 cells/microliter (1 × 106 total cells) resulted in a peak of ~600 mini-dystrophin positive myofibers in TA muscle single cross-sections. However, EDL muscles with up to 30% regional engraftment showed no functional improvements; similar limitations were obtained with whole muscle mononuclear cells. Despite the current lack of physiological improvement, this study suggests a viable initial strategy for using a patient-accessible dermal cell population to enhance skeletal muscle regeneration in DMD.

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Preclinical study of an ex vivo gene therapy protocol for hepatocarcinoma

Cited by 5 publications

References 43 publications

Hospicells (ascites‐derived stromal cells) promote tumorigenicity and angiogenesis

Hospicells (ascites‐derived stromal cells) promote tumorigenicity and angiogenesis

Gene Therapy for Pancreatic Cancer: Specificity, Issues and Hopes

Engraftment potential of dermal fibroblasts following in vivo myogenic conversion in immunocompetent dystrophic skeletal muscle

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