Gene Therapy for Ovarian Cancer Via Expression Of Intracellular Antibodies To Achieve Targeted Abrogation Of Selected Gene Product, Modulation of apoptosis and Molecular Therapy

Abstract

Ovarian cancer is a fatal disease with low curable rate by conventional therapy. -Recent advance in the molecular biology technology has allowed us to understand the 3cauired genetic lesions, which may contribute to development of ovarian cancer. Thus. gene therapy approach should be a logic step towards cure of this disease. In this study, different strategy of gene therapy has been explored in the context of ovarian cancer. The study is divided into laboratory part and a clinical part. The laboratory (preclinical part) we tried to explore mutation compensation strategy as mean to of gene therapy treatment in murine model of ovarian cancer. Then we further employ this strategy to enhance the effect of conventional therapy (radiation and chemotherapy) in human ovarian cell lines. We also explore the molecular chemotherapy strategy in the same animal model The clinical part involves two small studies on using these two-strategy to treat patient having ovarian cancer. Preclinical I-1.Production, Characterization and validation of single chain antibodies

(sFv)

The production of these sFv was done in collaboration with different labs. Validation and

Cytotoxic study has been confirmed.

To generate sFv, a hybridomas fusion cell lines was used as a sources of mRNA.data. "'- Validation of Scfvs against erbB-2, EGFR, Cyclin D1, bcl-2, LMP-1, CD20, IL-6R, and CA-125 has been made and sequenced and well characterized. Two of the sFv (EGFR