Adenovirus-mediated p53 gene transfer in patients with advanced recurrent head and neck squamous cell carcinoma.

Clayman, Gary L.; El‐Naggar, Adel K.; Lippman, Scott M.; Henderson, Ying C.; Frederick, Mitchell J.; Merritt, James A.; Zumstein, Louis; Timmons, Therese M.; Liu, Ta Jën; Ginsberg, Lawrence E.; Roth, Jack A.; Hong, Waun Ki; Bruso, Patricia A.; Goepfert, Helmuth

doi:10.1200/jco.1998.16.6.2221

Cited by 334 publications

(188 citation statements)

References 29 publications

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“…However, the presence of pre-existing antibodies did not correlate with tumour response. This finding agrees with the experience using non-replicating adenoviruses for the delivery of p53 into tumour cells, where a correlation between neutralizing antibodies and transgene delivery could not be established (Clayman et al, 1998).…”

Section: Clinical Experience Intratumoural Application Of Onyx-015supporting

confidence: 90%

ONYX-015: mechanisms of action and clinical potential of a replication-selective adenovirus

2002

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Accumulated knowledge in the molecular processes of tumour development combined with the availability of genetically modified viruses resemble the basis for new promising cancer therapeutics. The main advantages of employing replicationcompetent viruses are achievement of tumour selective killing and amplification of their oncolytic potential within the tumour mass. In this review, we describe the development of ONYX-015, one of the first and most advanced replication-competent viruses for cancer therapy. We discuss the molecular biology of this therapeutic approach and the interesting results obtained with this virus in clinical trials.

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Section: Clinical Experience Intratumoural Application Of Onyx-015supporting

confidence: 90%

ONYX-015: mechanisms of action and clinical potential of a replication-selective adenovirus

2002

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“…At most, the circulating Av1p53 could have directly infected 5-10% of the cells in this tumor. 37,47,55,60,72,73 To result in the complete elimination of the bFGF -BP signal we observed, every cell, theoretically, must have the gene downregulated. It is conceivable that by regulating the expression of another secreted intermediate (or more than one ), bFGF -BP expression was down -regulated in our system.…”

Section: Discussionmentioning

confidence: 96%

“…73 To determine what effect this disseminated virus might have on a tumor site distant from the inoculated tumor, in addition to the subcutaneous JSQ -3 xenograft tumor located on the upper right shoulder of the mouse, we also established a second xenograft tumor at a distant site on the mouse (on the lower left flank ). These tumors were distant enough from the injected tumor to most likely be free of any direct contact with the injected adenovirus.…”

Section: Effect Of Av1p53 Treatment On Distant Tumorsmentioning

confidence: 99%

Downmodulation of bFGF-binding protein expression following restoration of p53 function

et al. 2001

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Angiogenesis is a requirement for solid tumor growth. Therefore, inhibition of this neovascularization is one mechanism by which restoration of wtp53 function may lead to tumor regression. Here we report that adenoviral vector -mediated wild -type p53 transduction results in growth inhibition of squamous cell carcinoma of the head and neck tumor cells both in vitro and in a xenograft mouse model. This growth inhibition is associated with the down -regulation of the expression of fibroblast growth factor binding protein, a secreted protein required for the activation of angiogenic factor basic FGF. These findings suggest that wtp53 -induced tumor regression is due, at least in part, to antiangiogenesis mediated by the downmodulation of fibroblast growth factor binding protein. Cancer Gene Therapy ( 2001 ) 8, 771 -782

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“…Expression of the gene product is transient and phase I clinical trials have shown the virus to be safe and well tolerated at the highest doses of 10 11 PFU. [67][68][69][70][71][72][73] Studies have demonstrated the feasibility of both intravascular 74 and intratumoral 75 administration.…”

Section: Discussionmentioning

confidence: 99%

Adenovirus-mediated p53 gene therapy in pediatric soft-tissue sarcoma cell lines: sensitization to cisplatin and doxorubicin

et al. 2004

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Sarcomas, or tumors of connective tissue, represent roughly 20% of childhood cancers. Although the cure rate for sarcomas in general has significantly improved in the last 10 years, there continue to be subgroups that are difficult to treat. High-grade or metastatic soft-tissue sarcomas and rhabdomyosarcomas (RMS) of the extremities remain therapeutic challenges and their prognosis is often poor. The future of sarcoma therapy will likely include molecular approaches including gene/protein expression profiling and gene-based therapy. Most sarcomas harbor defects in the p53 or pRb pathways. The tumor suppressor p53 is central to regulation of cell growth and tumor suppression and restoring wild-type p53 function in pediatric sarcomas may be of therapeutic benefit. Studies with adenoviral-mediated p53 gene transfer have been conducted in many cancer types including cervical, ovarian, prostatic and head and neck tumors. Studies of this approach, however, remain limited in pediatric cancers, including sarcomas. Using three viral constructs containing cDNA for wild-type p53, mutant p53 (C135S) and lacZ, we studied the effect of adenoviralmediated gene therapy in four pediatric sarcoma cell lines, RD and Rh4 (RMS), Rh1 (Ewing's sarcoma) and A204 (undifferentiated sarcoma). Using the MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide) assay, we have shown a dose-dependent decrease in cell viability 72 h post-treatment that occurs with Ad-wtp53 but not with Ad-mutp53. Cells treated with Ad-wtp53 show upregulation of the p53 downstream targets, p21 CIP1/WAF1 and bax. Growth curves demonstrate suppression of cell growth over a period of 4 days and cells treated with Ad-wtp53 demonstrate a significant increase in sensitivity to the chemotherapeutic agents, cisplatin and doxorubicin. Our results indicate that restoration of wild-type p53 function in pediatric sarcoma cells could provide a basis for novel approaches to treatment of this disease.

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Adenovirus-mediated p53 gene transfer in patients with advanced recurrent head and neck squamous cell carcinoma.

Cited by 334 publications

References 29 publications

ONYX-015: mechanisms of action and clinical potential of a replication-selective adenovirus

ONYX-015: mechanisms of action and clinical potential of a replication-selective adenovirus

Downmodulation of bFGF-binding protein expression following restoration of p53 function

Adenovirus-mediated p53 gene therapy in pediatric soft-tissue sarcoma cell lines: sensitization to cisplatin and doxorubicin

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