Combination therapy with interleukin-2 and wild-type p53 expressed by adenoviral vectors potentiates tumor regression in a murine model of breast cancer

Human Gene Therapy
Brigitte M PützerF L Graham

Abstract

Although cytokine gene transfer for cancer treatment can stimulate immune recognition and tumor regression in animal models, there is still a need for improvements to these strategies. In this study, we examined the efficacy of a combination gene therapy using adenovirus (Ad) 5 vectors expressing human interleukin-2 and the wild-type (wt) human p53 gene under control of the human cytomegalovirus immediate early promoter (AdIL-2 and Adp53wt, respectively). Infected murine cell lines and primary mouse tumor cells secreted high levels of IL-2 and over expressed the p53 protein for at least 9 days. After infection of cells with Adp53wt, DNA synthesis was significantly inhibited and apoptosis was induced within 3-5 days. Both vectors were tested in a transgenic mouse mammary adenocarcinoma model for antitumor response. Following a single intratumoral injection of mice bearing PyMT induced tumors, the combination of Adp53wt (1 x 10(9) pfu) plus a relatively low dose of AdIL-2 (1.5 x 10(8) pfu) caused regressions in 65% of the treated tumors without toxicity. Fifty percent of the treated mice remained tumor free and were immune to rechallenge with fresh tumor cells. In contrast, injection of either vector alone at this does resulted i...Continue Reading

References

Jul 1, 1977·The Journal of General Virology·F L GrahamR Nairn
Oct 1, 1992·Proceedings of the National Academy of Sciences of the United States of America·D LinW E Mercer
Jan 1, 1991·Molecular and Cellular Biology·P JohnsonS Benchimol
Oct 1, 1990·The Journal of Experimental Medicine·B GansbacherE Gilboa
Nov 27, 1995·International Journal of Cancer. Journal International Du Cancer·C CirielliM C Capogrossi
Aug 29, 1995·Proceedings of the National Academy of Sciences of the United States of America·C L AddisonF L Graham
Mar 28, 1995·Proceedings of the National Academy of Sciences of the United States of America·S H ChenS L Woo
Mar 28, 1995·Proceedings of the National Academy of Sciences of the United States of America·W H SunN S Yang
May 9, 1995·Proceedings of the National Academy of Sciences of the United States of America·W SchmidtM L Birnstiel
Nov 1, 1994·Molecular and Cellular Biology·P M SiegelW J Muller
Sep 13, 1994·Proceedings of the National Academy of Sciences of the United States of America·A J BettF L Graham
Jan 1, 1993·Acta Oncologica·M G OrmerodG M Cohen
Aug 20, 1996·Proceedings of the National Academy of Sciences of the United States of America·P M Siegel, W J Muller
Oct 24, 1996·Gene·N K NavaniK L Dikshit
Apr 1, 1997·The Journal of General Virology·W QianK G Wiman
Apr 1, 1997·Gene Therapy·T OhnoG J Nabel
Jan 1, 1997·Advances in Pharmacology·G ParmianiF Arienti
Oct 6, 1997·Proceedings of the National Academy of Sciences of the United States of America·B M PützerF L Graham

❮ Previous
Next ❯

Citations

Aug 2, 2000·Proceedings of the National Academy of Sciences of the United States of America·Z Hu, A Garen
Sep 2, 2009·Microbiology and Molecular Biology Reviews : MMBR·Michele M Fluck, Brian S Schaffhausen
Apr 30, 2003·Expert Opinion on Biological Therapy·Sayon RoyAmy Chen
Jul 29, 2008·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Hironobu YanagieMasazumi Eriguchi
May 13, 2006·Critical Reviews in Oncology/hematology·Benjamin Pierre BouchetCarlos María Galmarini
Dec 25, 2004·Drug Metabolism and Pharmacokinetics·Shinsaku Nakagawa, Tadanori Mayumi
May 4, 2015·The Journal of Surgical Research·Barur R RajeshkumarGiles F Whalen
Oct 2, 2013·Oncoimmunology·Alexander SwarbrickMarcel Batten
Dec 18, 2004·Critical Reviews in Clinical Laboratory Sciences·Severine SeemannPierre Hainaut
Apr 9, 2017·Expert Opinion on Drug Delivery·Zhaolu Xie, Xianghui Zeng
Jun 8, 2002·Breast Cancer Research : BCR·Anneke C Blackburn, D Joseph Jerry
Oct 20, 2000·The Journal of General Virology·W C Russell
Dec 19, 1998·Journal of Interferon & Cytokine Research : the Official Journal of the International Society for Interferon and Cytokine Research·P C EmtageJ Gauldie
Mar 16, 2001·Breast Cancer Research : BCR·J Gómez-NavarroJ Xiang

❮ Previous
Next ❯

Related Concepts

Related Feeds

Breast Tumorigenesis

Breast tumorigenesis involves the production or formation of tumor(s) in breast tissue. Discover the latest research on breast tumorigenesis here.

CREs: Gene & Cell Therapy

Gene and cell therapy advances have shown promising outcomes for several diseases. The role of cis-regulatory elements (CREs) is crucial in the design of gene therapy vectors. Here is the latest research on CREs in gene and cell therapy.

Apoptosis

Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis