Development of Anti-GLUT-1 Antibody as a Novel Therapeutic Strategy Against Breast Cancer

摘要

In the work outlined in the grant we propose to show that anti-Glut- 1 antibodies can kill breast cancer cells in vivo. We have previously demonstrated that anti- glut-1 antibodies can kill breast cancer cell lines in vitro. Since the funding was initiated, we have further worked out the mechanisms by which anti-glut-1 antibodies killa cancer cells. We have since demonstrated that glut-1 antibodies, secondary to decreased glucose entry, reduces intracellular ATP generation consequently leading to increased pAMPK generation which acts as an energy sensor in the cell. pAMPK also has tumor suppressor properties Therefore leading to the up regulation of proapoptotic proteins BCL-XL and BAD and down regulation of anti-apoptotic proteins survivin and XIAP. Please see the attached figures. We have also shown that treatment with anti-glut-1 antibody decrease epithelial-mesenchymal transition (As seen in Figure 6). Since the P.I. has accepted a position as senior member at the Fox Chase Cancer Center, in Philadelphia PA further work will continue there. To initiate work on specific aim 1 and 2, the P.I. tested several commercially available antibodies and found these antibodies to be largely un-reliable in it's ability to detect the glut-I antibody. Further testing continues. At the Fox Chase Cancer Center, there is core that generates antibodies. The P.I. has decided to generate our own antibodies which would be more reliable in its function and enable us to generate good data and pursue proof of principle of studies. The generation of these antibodies will be funded by the Fox Chase Cancer Center as part of the recruitment package given to the P.I. Once the new antibodies have been generated then we plan to proceed with specific aims one and two. It is anticipated that the antibodies will be available by Feb 09.