Anti-PSCA mAbs inhibit tumor growth and metastasis formation and prolong the survival of mice bearing human prostate cancer xenografts

Prostate stem-cell antigen (PSCA) is a cell-surface antigen expressed in no rmal prostate and overexpressed in prostate cancer tissues. PSCA expression is detected in over 80% of patients with local disease, and elevated level s of PSCA are correlated with increased tumor stage, grade, and androgen in dependence, including high expression in bone metastases. We evaluated the therapeutic efficacy of anti-PSCA mAbs in human prostate cancer xenograft m ouse models by using the androgen-dependent LAPC-9 xenograft and the androg en-independent recombinant cell line PC3-PSCA. Two different anti-PSCA mAbs , 1G8 (IgG1 kappa) and 3C5 (IgG2a kappa), inhibited formation of s.c. and o rthotopic xenograft tumors in a dose-dependent manner. Furthermore, adminis tration of anti-PSCA mAbs led to retardation of established orthotopic tumo r growth and inhibition of metastasis to distant sites, resulting in a sign ificant prolongation in the survival of tumor-bearing mice. These studies s uggest PSCA as an attractive target for immunotherapy and demonstrate the t herapeutic potential of anti-PSCA mAbs for the treatment of local and metas tatic prostate cancer.