Expression of Transforming Growth Factor-Beta (TGF-Beta) in Prostate Cancer Cell Progression

摘要

The objective of the current Phase II proposal is to test a novel TGF-beta based gene therapy in prostate cancer. During the Phase I study, our findings demonstrate that TGF-beta over-production by the tumor cells was immunosuppressive. In the Phase II research we proposed to render host immune cells insensitive to TGF-beta by introducing a domina negative TGF-beta type II receptor (dnTBRII) to host immune cells. Three tasks were proposed. In Task 1, we proposed to generate the dnTBRII construct with green fluoresce protein (GFP) as a selectable marker and introduce the construct into host's bone marro cells. In Task 2, we proposed to test if immune cells will escape the negative selection in the thymus. In Task 3, we proposed to test whether or not the TGF- beta insensitive immune cells will mediate anti-tumor activity.