Journal of Bioequivalence & Bioavailability

Anti-PSMA antibodies and fragments for diagnosis and therapy of prostate cancer

International Conference and Exhibiton on Pharmaceutical Regulatory Affairs

6-7 September 2011 Baltimore, USA

Ursula Elsasser-Beile

Scientific Tracks Abstracts: JBB

Abstract:

T he Prostate Specifi c Membrane Antigen (PSMA) represents an excellent target for diagnosis and therapy of prostate cancer. PSMA is specifi cally expressed in high density as a homodimer on the surface of prostate epithelial cells. It is upregulated in all stages of prostate cancer, not secreted into the circulation and internalized aft er antibody binding. Recently, we have generated three monoclonal antibodies (mAbs) and single chain antibody fragments (scFv) that react with cell-adherent PSMA and bind with a high affi nity to PSMA- expressing prostate cancer cells. From these mAbs two single chain antibody fragments were developed by phage display. Th eir binding pattern was comparable to the parental antibodies. As diagnostic tools, we used the 64 Cu-DOTA-labelled mAbs for imaging of prostate cancer xenograft s in SCID mice. Static small-animal PET images of mice with PSMA-positive tumors revealed a high tumor-to-background ratio. In contrast, no signifi cant tracer uptake was observed in the PSMA-negative DU 145 tumors. As therapeutic tools, we have generated recombinant immunotoxins with a truncated form of pseudomonas Exotoxin A as toxic domain attached to the scFv as binding domain. Th ese immunotoxins showed a high and specifi c cytotoxicity against PSMA-expressing C4-2 prostate cancer cells in vitro and a growth inhibition of human C4-2 Xenograft s in SCID mice in vivo . Due to the specifi c binding to prostate cancer cells and their high uptake in PSMA-positive tumors our mAbs and scFv bear a high potential for diagnosis and therapy.