Phase I/II Marker Lesion Study of Intravesical BC-819 DNA Plasmid in H19 Over Expressing Superficial Bladder Cancer Refractory to Bacillus Calmette-Guerin

Sidi, Avner; Ohana, Patricia; Benjamin, Shalva; Shalev, Moshe; Ransom, Janet H.; Lamm, Donald L.; Hochberg, Avraham; Leibovitch, Ilan

doi:10.1016/j.juro.2008.08.006

Cited by 129 publications

(84 citation statements)

References 16 publications

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“…For systemic in vivo delivery, transfection agents based on polyethylenimine (PEI) have shown the most promise (18,19). One of the most effective formulations, in vivo-jetPEI (Polyplus Transfection), has been evaluated for gene delivery in a number of cancer models in vivo (20)(21)(22)(23)(24)(25)(26), although rarely via systemic injection (27)(28)(29), as well as in several clinical trials for heart disease (30), HIV (31), and cancer (32). Because s.c. tumor models might not faithfully reflect the architecture of internal tumors, we elected to use a model established by intrasplenic injection of the HCT116 line of human colorectal cancer cells in NOD-SCID-IL-2Rγ-deficient mice (NOG mice) (33).…”

Section: Resultsmentioning

confidence: 99%

A nanoparticle formulation that selectively transfects metastatic tumors in mice

Yang

Hendricks

Liu

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

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Nanoparticle gene therapy holds great promise for the treatment of malignant disease in light of the large number of potent, tumorspecific therapeutic payloads potentially available for delivery. To be effective, gene therapy vehicles must be able to deliver their therapeutic payloads to metastatic lesions after systemic administration. Here we describe nanoparticles comprised of a core of high molecular weight linear polyethylenimine (LPEI) complexed with DNA and surrounded by a shell of polyethyleneglycol-modified (PEGylated) low molecular weight LPEI. Compared with a stateof-the-art commercially available in vivo gene delivery formulation, i.v. delivery of the core/PEGylated shell (CPS) nanoparticles provided more than a 16,000-fold increase in the ratio of tumor to nontumor transfection. The vast majority of examined liver and lung metastases derived from a colorectal cancer cell line showed transgene expression after i.v. CPS injection in an animal model of metastasis. Histological examination of tissues from transfected mice revealed that the CPS nanoparticles selectively transfected neoplastic cells rather than stromal cells within primary and metastatic tumors. However, only a small fraction of neoplastic cells (<1%) expressed the transgene, and the extent of delivery varied with the tumor cell line, tumor site, and host mouse strain used. Our results demonstrate that these CPS nanoparticles offer substantial advantages over previously described formulations for in vivo nanoparticle gene therapeutics. At the same time, they illustrate that major increases in the effectiveness of such approaches are needed for utility in patients with metastatic cancer.

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Section: Resultsmentioning

confidence: 99%

A nanoparticle formulation that selectively transfects metastatic tumors in mice

Yang

Hendricks

Liu

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

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“…Intratumoral injections of BC-819 (DTA-H19) plasmid, which carries the gene for the A subunit of diphtheria toxin under the regulation of the H19 promoter, induce the expression of high levels of diphtheria toxin specifically in the tumor resulting in a reduction of tumor size in human trials. Recent studies have yielded encouraging results in a wide range of carcinomas including NSCLC, colon, bladder, pancreatic and ovarian cancers (Amit and Hochberg;Hasenpusch et al;Smaldone and Davies;Sidi et al, 2008;Mizrahi et al, 2009). The successful trial undoubtedly gives us a faith and good method for the treatment of RCC through manipulating the expression of GAS5 in vivo.…”

Section: Discussionmentioning

confidence: 99%

Long Non-coding RNA GAS5 Functions as a Tumor Suppressor in Renal Cell Carcinoma

Qiao¹,

Gao²,

Huo³

et al. 2013

Asian Pacific Journal of Cancer Prevention

212

152

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Background: Renal cell carcinoma (RCC) is a malignancy with a poor prognosis. We aimed to explore whether the expression of Long Non-Coding RNA (LncRNA) growth arrest-specific transcript 5 (GAS5) is associated with RCC genesis. Methods: We selected twelve clinical samples diagnosed for renal clear cell carcinoma and found that the LncRNA GAS5 transcript levels were significantly reduced relative to those in adjacent unaffected normal renal tissues. Results: In addition, expression of GAS5 was lower in the RCC cell line A498 than that in normal renal cell line HK-2. Furthermore, using functional expression cloning, we found that overexpression of GAS5 in A498 cells inhibited cell proliferation, induced cell apoptosis and arrested cell cycling. At the same time, the migration and invasion potential of A498 cells were inhibited compared to control groups. Conclusion: Our study provided the first evidence that a decrease in GAS5 expression is associated with RCC genesis and progression and overexpression of GAS5 can act as a tumor suppressor for RCC, providing a potential attractive therapeutic approach for this malignancy.

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“…Amongst several transfection agents explored in clinical studies so far [11,12], the supramolecular cationic cyclodextrin polymers have also yielded appreciable results [13].…”

Section: Introductionmentioning

confidence: 99%

Cellular delivery of polynucleotides by cationic cyclodextrin polyrotaxanes

Dandekar

Jain

Keil

et al. 2012

Journal of Controlled Release

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Cationic polyrotaxanes, obtained by temperature activated threading of cationic cyclodextrin derivatives onto water soluble cationic polymers (ionenes), form metastable nanometric polyplexes with pDNA and combinations of siRNA with pDNA.Because of their low toxicity, the polyrotaxane polyplexes constitute a very interesting system for the transfection of polynucleotides into mammalian cells. The complexation of Cy3-labeled siRNA within the polyplexes was demonstrated by fluorescence correlation spectroscopy. The uptake of the polyplexes (red) was imaged by confocal fluorescence microscopy using the A549 cell line as a model (blue: nuclei, green: membranes). The results prove the potential of polyrotaxanes for further investigations involving knocking down genes of therapeutic interest.

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Phase I/II Marker Lesion Study of Intravesical BC-819 DNA Plasmid in H19 Over Expressing Superficial Bladder Cancer Refractory to Bacillus Calmette-Guerin

Abstract: Intravesical BC-819 causes tumor ablation following intravesical administration at doses that were well tolerated. It is worthy of continued clinical investigation.

Cited by 129 publications

References 16 publications

A nanoparticle formulation that selectively transfects metastatic tumors in mice

A nanoparticle formulation that selectively transfects metastatic tumors in mice

Long Non-coding RNA GAS5 Functions as a Tumor Suppressor in Renal Cell Carcinoma

Cellular delivery of polynucleotides by cationic cyclodextrin polyrotaxanes

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