Ovarian Cancer Gene Therapy

Tait, David L.; Obermiller, Patrice S.; Jensen, Roy A.; Holt, Jeffrey T.

doi:10.1016/s0889-8588(05)70007-1

Cited by 14 publications

(10 citation statements)

References 29 publications

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“…To this end, a variety of gene therapy trials for ovarian cancer have been approved and several are underway (Anonymous, 1999). These include virus-mediated delivery of the herpes simplex virus thymidine kinase gene in a suicide gene therapy approach , Tong et al, 1996, delivery of tumor suppressor genes such as p53 (Mujoo et al, 1996) and BRCA1 (Tait et al, 1998) for mutation compensation, and delivery of a gene encoding a single-chain intracellular antibody directed against p185/erbB-2 for HER-2/neu-overexpressin g tumors Deshane et al, 1997). The success of any of these approaches is dependent on efficient in vivo delivery of the therapeutic gene.…”

Section: Introductionmentioning

confidence: 99%

Using a Tropism-Modified Adenoviral Vector to Circumvent Inhibitory Factors in Ascites Fluid

Blackwell

Gómez-Navarro

et al. 2000

Human Gene Therapy

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Peritoneal compartmentalization of advanced stage ovarian cancer provides a rational scenario for gene therapy strategies. Several groups are exploring intraperitoneal administration of adenoviral (Ad) vectors for this purpose. We examined in vitro gene transfer in the presence of ascites fluid from ovarian cancer patients and observed significant inhibition of Ad-mediated gene transfer. The inhibitory activity was not identified as either complement or cellular factors, but depletion of IgG from ascites removed the inhibitory activity, implicating neutralizing anti-Ad antibodies. A wide range of preexisting anti-Ad antibody titers in patient ascites fluid was measured by ELISA. Western blot analysis demonstrated that the antibodies were directed primarily against the Ad fiber protein. To circumvent inhibition by neutralizing antibodies, a genetically modified adenoviral vector was tested. The Ad5Luc.RGD vector has an Arg-Gly-Asp (RGD) peptide sequence inserted into the fiber knob domain and enters cells through a nonnative pathway. Compared with the conventional Ad5 vector, Ad5Luc.RGD directed efficient gene transfer to cell lines and primary ovarian cancer cells in the presence of ascites fluid containing high-titer neutralizing anti-Ad antibodies. These results suggest that such modified Ad vectors will be needed to achieve efficient gene transfer in the clinical setting.

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Section: Introductionmentioning

confidence: 99%

Using a Tropism-Modified Adenoviral Vector to Circumvent Inhibitory Factors in Ascites Fluid

Blackwell

Gómez-Navarro

et al. 2000

Human Gene Therapy

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“…The metastasis of ovarian cancer is generally confined to the abdominal cavity, which has made ovarian cancer a good candidate for local gene therapy via intraperitoneal administration 17 18 . Indeed, ovarian cancer has been an important target in the field of human gene therapy over the past 20 years 19 20 , and we are developing such a potential therapy.…”

mentioning

confidence: 99%

Ovarian cancer treatment with a tumor-targeting and gene expression-controllable lipoplex

Deng

Wei

et al. 2016

Sci Rep

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Overexpression of folate receptor alpha (FRα) and high telomerase activity are considered to be the characteristics of ovarian cancers. In this study, we developed FRα-targeted lipoplexes loaded with an hTERT promoter-regulated plasmid that encodes a matrix protein (MP) of the vesicular stomatitis virus, F-LP/pMP(2.5), for application in ovarian cancer treatment. We first characterized the pharmaceutical properties of F-LP/pMP(2.5). The efficient expression of the MP-driven hTERT promoter in SKOV-3 cells was determined after an in-vitro transfection assay, which was significantly increased compared with a non-modified LP/pMP(2.5) group. F-LP/pMP(2.5) treatment significantly inhibited the growth of tumors and extended the survival of mice in a SKOV-3 tumor model compared with other groups. Such an anti-tumor effect was due to the increased expression of MP in tumor tissue, which led to the induction of tumor cell apoptosis, inhibition of tumor cell proliferation and suppression of tumor angiogenesis. Furthermore, a preliminary safety evaluation demonstrated a good safety profile of F-LP/pMP(2.5) as a gene therapy agent. Therefore, FRα-targeted lipoplexes with therapeutic gene expression regulated by an hTERT promoter might be a promising gene therapy agent and a potential translational candidate for the clinical treatment of ovarian cancer.

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“…Initial studies of a BRCA1 retroviral vector employed a complementary DNA that encoded a splice variant vector that eliminates the first 71 amino acids of the human protein, termed BRCA1sv [2,25,36*]. Studies of both growth inhibition and DNA repair do not identify cellular or molecular differences between BRCA1sv and BRCA1 complementary DNAs [36*,37,38,39,40]. Intaperitoneal injection of either BRCA1sv or a full-length BRCA1 retroviral vector into ovarian cancer or breast cancer xenografts in nude mice produces tumor inhibition [2,15,25,36*,37,38,39].…”

Section: Brca1 Gene Therapymentioning

confidence: 99%

“…Studies of both growth inhibition and DNA repair do not identify cellular or molecular differences between BRCA1sv and BRCA1 complementary DNAs [36*,37,38,39,40]. Intaperitoneal injection of either BRCA1sv or a full-length BRCA1 retroviral vector into ovarian cancer or breast cancer xenografts in nude mice produces tumor inhibition [2,15,25,36*,37,38,39]. These studies show that treatment of established SKOV3 or PA-1 ovarian cancer nude mice xenografts with either the full-length or the splice variant BRCA1 retroviral vector results in tumor suppression.…”

Section: Brca1 Gene Therapymentioning

confidence: 99%

“…Necropsies showed that PA-1 tumor-bearing mice treated with control media or low-dose LXSN- BRCA1sv died with large intra-abdominal tumors and ascites, whereas mice with high-dose LXSN- BRCA1sv treatments died of lung metastasis with significantly smaller abdominal tumor. The PA-1 tumor model is an established xenograft model for ovarian cancer [37,38,39,41,42]. …”

Section: Brca1 Gene Therapymentioning

confidence: 99%

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Gene therapy for carcinoma of the breast: Therapeutic genetic correction strategies

1999

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Gene therapy is a therapeutic approach that is designed to correct specific molecular defects that contribute to the cause or progression of cancer. Genes that are mutated or deleted in cancers include the cancer susceptibility genes p53 and BRCA1. Because mutational inactivation of gene function is specific to tumor cells in these settings, cancer gene correction strategies may provide an opportunity for selective targeting without significant toxicity for normal nontumor cells. Both p53 and BRCA1 appear to inhibit cancer cells that lack mutations in these genes, suggesting that the so-called gene correction strategies may have broader potential than initially believed. Increasing knowledge of cancer genetics has identified these and other genes as potential targets for gene replacement therapy. Initial patient trials of p53 and BRCA1 gene therapy have provided some indications of potential efficacy, but have also identified areas of basic and clinical research that are needed before these approaches may be widely used in patient care.

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Ovarian Cancer Gene Therapy

Cited by 14 publications

References 29 publications

Using a Tropism-Modified Adenoviral Vector to Circumvent Inhibitory Factors in Ascites Fluid

Using a Tropism-Modified Adenoviral Vector to Circumvent Inhibitory Factors in Ascites Fluid

Ovarian cancer treatment with a tumor-targeting and gene expression-controllable lipoplex

Gene therapy for carcinoma of the breast: Therapeutic genetic correction strategies

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