Assessment of p53 Gene Transfer and Biological Activities in a Clinical Study of Adenovirus-p53 Gene Therapy for Recurrent Ovarian Cancer

Cancer Gene Therapy volume 10, pages 224–238 (2003), DOI10.1038/sj.cgt.7700562

Posted: 17 Apr 2019

Date Written: March 14, 2003

Abstract

A cohort study was designed to evaluate the efficiency of gene transfer and whether biological activity from the expressed therapeutic gene resulted after administration of a recombinant adenovirus containing the human wild-type p53 (p53wt) gene (rAd-p53 SCH 58500). The cohort study was conducted in five trial subjects with recurrent ovarian cancer. Each trial subject received multiple cycles of rAd-p53 SCH 58500, each cycle comprised of doses of 7.5 × 1013 particles on each of five consecutive days. Subjects were treated with rAd-p53 SCH 58500 alone during Cycle 1 and in combination with gemcitabine during the subsequent cycles. Both tumor biopsies and peritoneal aspirates were collected and evaluated for gene transfer and evidence of the biological activities of the expressed p53wt gene. Using quantitative PCR and RT-PCR, and in situ PCR, gene transfer and expression were documented in tumor biopsies (four of five patients) collected from Cycle 1. Furthermore, upregulation of p21/WAF1, bax and mdm-2, and downregulation of survivin were observed in these same tumor biopsy samples, suggesting that intraperitoneal administration of rAd-p53 SCH 58500 leads to detectable p53 biological activity in target tumor tissue. In addition, gene transfer and its expression were observed in cells obtained from peritoneal aspirates. These fluids were mainly comprised of polymorphonuclear neutrophils, indicating that successful gene transfer can be achieved by multiple cycle intraperitoneal administration of recombinant adenovirus.

Keywords: gene therapy, cancer, p53, p21

Suggested Citation

Shinoda, Jeremy, Assessment of p53 Gene Transfer and Biological Activities in a Clinical Study of Adenovirus-p53 Gene Therapy for Recurrent Ovarian Cancer (March 14, 2003). Cancer Gene Therapy volume 10, pages 224–238 (2003), DOI10.1038/sj.cgt.7700562. Available at SSRN: https://ssrn.com/abstract=3361752

Jeremy Shinoda (Contact Author)

Cordant Health Solutions ( email )

United States

HOME PAGE: http://www.cordantsolutions.com

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