Journal of Bioequivalence & Bioavailability

Preclinical evaluation of a PSMAxCD3 Diabody for therapy of prostate cancer

International Conference and Exhibiton on Pharmaceutical Regulatory Affairs

6-7 September 2011 Baltimore, USA

Patrick Buhler

Scientific Tracks Abstracts: JBB

Abstract:

A lthough prostate cancer is the most commonly diagnosed cancer in men and second leading cancer-related cause of death in the Western Civilization there is currently no curative option for advanced stages. A new approach in cancer therapy has been the retargeting of T-cells to the tumor cells by bispecifi c recombinant antibody fragments, termed diabodies. We have constructed a PSMAxCD3 diabody directed against the prostate specifi c membrane antigen (PSMA) on prostate cancer cells and the epsilon-chain of CD3 on T-cells. In the present study, the eff ectivity of the diabody was characterized in vitro and in vivo. Aft er expression into the periplasm of XL-1 Blue E.coli bacteria, the diabody was purifi ed by Immobilized Metal Affi nity Chromatography (IMAC). For determining the cytotoxic potential, PSMA-positive C4-2 cells were incubated with CD4+ and CD8+ lymphocytes. Lysis of the C4-2 cells was measured by a WST-1 assay. Our study proves that the PSMAxCD3 diabody is very potent in eliminating PSMA-positive pros tate cancer cells by redirected lysis through CD3-positive T-lymphocytes in vitro . In a SCID mouse model with C4-2 xenograft tumors, the diabody together with human peripheral blood lymphocytes effi ciently inhibited tumor growth. Th e results suggest the diabody to be a powerful agent which could contribute to an eff ective new therapy against prostate cancer

Biography :

Patrick B?hler has completed his Ph.D at the age of 31 years from Freiburg University and continued to do postdoctoral research as research associate. He has published 19 papers in reputed journals