第２回 国際癌治療増感研究協会
国際研究奨励賞

＜研究テーマ＞

Developement of tumor-specific gene therapy system using hypoxia-inducible vectors: Sensitization of radiation effects in tumor models

Runjiang Qu (曲 潤江) 氏

Department of Radiation Medicine,
Xi'an Medical University(中国)

＜Brief Career History＞

＜Title of Study＞

Developement of tumor-specific gene therapy system using hypoxia-inducible vectors: Sensitization of radiation effects in tumor

＜Purpose＞

Hyposic cells in solid tumors have been regarded as a cause of radioresistance of cancers. Utilization of hypoxia responsive element (HRE) derived from the human VEGF gene may provide a new avenue to activate genes specifically in the hypoxic solid tumors both in diagnostic and therapeutic strategies. We are developing experimental gene therapy models based on HRE system, especially for enhancement of combination effects with radiotherapy.

＜Methods＞

1. We need to generate hypoxia-inducible vectors expressing prodrug activating enzymes, such as E. coli cytosine deaminase, nitroreductase, and purine nucleotide phosphorylase.
2. Modifications of the vectors should be done for enough levels of gene expression to achieve effective antitumor effects both in vitro and in vivo experimental models.
3. We are also going to construct GFP expression vectors under control of the same expression unit to detect and monitor tumor-specific gene expression in the hypoxic areas.
4. Combination of radiotherapy and prodrug would be applied to tumor bearing mice to examine efficacy of these gene therapy strategies.

＜Expected Result＞

Improvement of hypoxic tumor cell killing would result in enhancement of tumor control by combination of gene therapy and radiotherapy. Establishment of experimental gene therapy system targeting hypoxia would help future application of these strategies to the clinic for radioresistant cancers.

＜Study Plan in the Future＞

Further studies are undergoing in international collaboration with Kyoto University (Dr. T. Shibata) and Stanford University (Dr. J. Martin, Brown).
1. Effective gene delivery system should be selected, including liposome-mediated or viral versions of gene transfer methods with determination of optimal combination of prodrug activation system and radiation. Experimantal and preclinical evaluation would be done both in terms of efficacy and safety of these combined gene therapy with radiotherapy.
2. Hypoxia-inducible GFP-expression would enable us to visualize hypoxic fractions of solid tumors. This may be also a good tool to monitor levels of tumor hypoxia in real time in various situations including experimental systems.

＜連絡先＞

Runjiang Qu (曲 潤江)
Department of RadiationMedicine,
Xi'an Medical University
17#Changle West Road, Xi'an, China,
Postal Code: 710032
TEL: 075-751-3419
FAX: 075-771-9749