期刊
GENE THERAPY
卷 16, 期 6, 页码 796-804出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/gt.2009.14
关键词
NDV; oncolytic; interleukin-2; cancer; virotherapy
类别
资金
- Northeast Biodefense [U54 AI057158]
- NIH [T32AI07647]
- Mount Sinai Department of Medicine Training
- Bill and Melinda Gates Foundation [38648]
- Flight Attendant Medical Research Institute
- Mount Sinai School of Medicine
- NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES [T32AI007647, U54AI057158] Funding Source: NIH RePORTER
Despite the advances in cancer therapies in the past century, malignant melanoma continues to present a significant clinical challenge due to lack of chemotherapeutic response. Systemic therapy with immunostimulatory agents such as interferon and interleukin-2 (IL-2) has shown some promise, though each is associated with significant side effects. Over the past 50 years, oncolytic Newcastle disease virus (NDV) has emerged as an alternative candidate for cancer therapy. The establishment of reverse-genetics systems for the virus has allowed us to further manipulate the virus to enhance its oncolytic activity. Introduction of immunomodulatory molecules, especially IL-2, into the NDV genome was shown to enhance the oncolytic potential of the virus in a murine syngeneic colon carcinoma model. We hypothesize that a recombinant NDV expressing IL-2 would be an effective agent for therapy of malignant melanoma. We show that recombinant NDV possesses a strong cytolytic activity against multiple melanoma cell lines, and is effective in clearing established syngeneic melanoma tumors in mice. Moreover, introduction of murineIL- 2 into NDV significantly enhanced its activity against syngeneic melanomas, resulting in increased overall animal survival and generation of antitumor immunity. These findings warrant further investigations of IL-2-expressing NDV as an antimelanoma agent in humans. Gene Therapy (2009) 16, 796-804; doi:10.1038/gt.2009.14; published online 26 February 2009
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