Cancer gene therapy using a novel adeno-associated virus vector expressing human wild-type p53

Qazilbash, Muzaffar H.; Xiao, Xianmin; Seth, Prem; Cowan, Kenneth H.; Walsh, Christopher E.

doi:10.1038/sj.gt.3300444

Cited by 44 publications

(34 citation statements)

References 12 publications

(16 reference statements)

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“…Adenovirus and retrovirus vectors have been the leading candidates for cancer gene therapy, 1,2 and adeno-associated virus has also proved successful in the transduction of this tumour suppresser gene. 3 Inactivation of p53 has been implicated in many types of tumour, 4 and non-small cell lung carcinoma (NSCLC) is one of the most common human cancers in which p53 mutations have been frequently identified. However, not all tumours are amenable to therapy with p53, and there is a need for the development of vectors which induce apoptosis independently of p53.…”

Section: Introductionmentioning

confidence: 99%

Inhibition of human lung carcinoma cell growth by apoptosis induction using Semliki Forest virus recombinant particles

et al. 2000

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We have utilised cell cultures and growth of tumours in nude mice to assess further the potential of the Semliki Forest virus (SFV) vector as a cancer therapy agent. This vector is a transient RNA-based expression vector, and we have previously shown that SFV and its derived vector can induce p53-independent apoptosis by expression of the nonstructural region of the virus genome. Apoptosis induction is therefore an inherent property of the vector and is not dependent on heterologous gene expression. SFV recombinant suicide particles (rSFV) were shown to induce apoptosis in H358a cells, which are human non-small cell lung carcinoma cells deleted in p53. EGFP-expressing rSFV

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Section: Introductionmentioning

confidence: 99%

Inhibition of human lung carcinoma cell growth by apoptosis induction using Semliki Forest virus recombinant particles

et al. 2000

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“…As expected, the inhibitory effect of rAAV-p53 was mediated by apoptosis. 27 Encouraged from the results that wild-type AAV-2 itself as well as p53 can enhance the sensitivity to chemotherapy, we were interested if recombinant AAV-2 vectors have the same ability. Combined treatment of NSCLC cell lines with cisplatin and recombinant AAV-p53 led to additive or overadditive inhibitory effects on lung tumor cells with a growth inhibition between 81 and 91%.…”

Section: Discussionmentioning

confidence: 99%

Non-small lung cancer cells are prime targets for p53 gene transfer mediated by a recombinant adeno-associated virus type-2 vector

et al. 2003

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In this study, we elucidated the potential of recombinant adeno-associated virus type-2 (rAAV-2) vectors for lung cancer gene therapy. Cell lines of the three major histological subtypes of non-small cell lung cancer (NSCLC) were highly susceptible for rAAV-2 showing transduction rates between 63.4 and 98.9%. In contrast, cell lines of small cell carcinomas were resistant to rAAV-2 infection. For restoration of p53 function in p53 deficient NSCLC, a rAAV-2 vector was constructed containing wt p53 cDNA. Following transduction with rAAV-p53, cell growth of all NSCLC cell lines was significantly reduced in a dose-dependent manner between 44 and 71.7% in comparison with rAAV-GFP transduced cells. The reduction of tumor cell growth was associated with increased apoptosis. Adding cisplatin to rAAV-p53-infected cells led to a significant growth inhibition between 81 and 91% indicating a synergistic effect between cisplatin and rAAV-p53. Interestingly, the tumor cells surviving cisplatin and rAAV-p53 treatment were inhibited in their ability to form colonies as reflected by a reduction of colony growth between 57 and 90.4%. In conclusion, rAAV-2 vectors exhibit a strong tropism for NSCLC. Successful inhibition of tumor cell growth following transduction with a rAAV-p53 vector underlines the potential role of rAAV-2 in cancer gene therapy.

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“…52 K562 (human erythroleukemia) and Renca (mouse renal cell carcinoma) cells were maintained at 37°C, 5% CO 2 in RPMI 1640 media (Life Technologies, Gaithersburg, MD) supplemented with 10% fetal bovine serum and antibiotics (50 g/mL gentamicin, 100 g/mL penicillin, and 2.5 g/mL fungisone). The plasmids pAAV/Ad, 52 pRep4, 52 and p008Sub/NeoR 53 have been described previously.…”

Section: Cell Lines and Plasmidsmentioning

confidence: 99%

“…53 After a 16-hour incubation (37°C, 5% CO 2 ), the Opti-Mem I (Life Technologies) medium containing no supplements was replaced with RPMI 1640 medium supplemented with 2% fetal bovine serum and antibiotics. The 293 cells were harvested 72 hours later by scraping, centrifuged (500 ϫ g, 5 minutes), resuspended in 20 ml of phosphate buffered saline (PBS), and sonicated (three 20-second bursts, output control 5, duty cycle 50%).…”

Section: Cell Lines and Plasmidsmentioning

confidence: 99%

Construction of a recombinant adeno-associated virus (rAAV) vector expressing murine interleukin-12 (IL-12)

Paul¹,

Qazilbash²,

Song³

et al. 2000

Cancer Gene Ther

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IL-12 is a heterodimeric cytokine that is known to induce tumor regression and long-term antitumor immunity. Recombinant adeno-associated virus (rAAV) vectors are advantageous for gene therapy in that they lack pathogenicity in humans, infect dividing as well as nondividing cells, and show a broad range of infectivity. We constructed an rAAV vector expressing interleukin-12 (IL-12) for cancer immunotherapy studies in a mouse model by inserting murine IL-12 (mIL-12) p35 and p40 cDNAs into the plasmid pRep4 and inserting the encephalomyocarditis virus internal ribosomal entry site between the p35 and p40 cDNAs. The mIL-12 expression cassette containing the Rous sarcoma virus promoter and a simian virus 40 polyadenylation signal was subcloned into the AAV plasmid p008Sub/NeoR, which contains two AAV inverted terminal repeat sequences and the NeoR gene driven by the thymidine kinase promoter. rAAV virions (10 4 infectious particles/ml) were generated by cotransfection of rAAV-mIL-12 and a helper plasmid (pAAV/Ad) into 293 cells previously infected with adenovirus 5. After infection of D6 fibroblasts with rAAV-mIL-12, G418-resistant clones were isolated. Each of the 1D D6 clones isolated produced up to 5.2 ng/10 6 cells/48 hours of mIL-12 as determined by enzyme-linked immunosorbent assay. Induction of interferon-␥, enhanced lymphocyte proliferation, and cytotoxicity assays confirmed biologically functional IL-12 production by the vector. This is the first report indicating that an rAAV vector expresses mIL-12, which can be used to model the effects of mIL-12 alone and/or in combination with other antitumor agents. Cancer Gene Therapy (2000) 7, 308 -315

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Cancer gene therapy using a novel adeno-associated virus vector expressing human wild-type p53

Cited by 44 publications

References 12 publications

Inhibition of human lung carcinoma cell growth by apoptosis induction using Semliki Forest virus recombinant particles

Inhibition of human lung carcinoma cell growth by apoptosis induction using Semliki Forest virus recombinant particles

Non-small lung cancer cells are prime targets for p53 gene transfer mediated by a recombinant adeno-associated virus type-2 vector

Construction of a recombinant adeno-associated virus (rAAV) vector expressing murine interleukin-12 (IL-12)

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