Mechanism of Action of Prostate Stem Cell Antigen Targeted Antibody Therapy and Its Relevance to Clinical Application in Prostate Cancer

摘要

We have recently demonstrated that a monoclonal antibody against prostate stem cell antigen (PSCA) can exert anti-tumor activity in a xenograft animal model, suggesting oncogenic activity of PSCA in prostate cancer. Therefore our goal is to elucidate the role of PSCA in the development of prostate cancer. A better understanding of PSCA function and its antibody activity will enable rational patient selection and trial design, all of which are particularly relevant to subsequent clinical trials of PSCA antibody. Better insight into the function of PSCA were obtained from the PSCA overexpressing experiments. We showed that PSCA promote significant cell growth as well as anchorage independent growth in prostate cancer cell line 22RV1, compared to that of normal cell line PZ-HPV7. Furthermore, PSCA appears to confer resistance to anoikis in both cell lines 22RV1 and LNCaP. These findings suggest that PSCA may enhance growth and survival of prostate tumor cells, particularly in the context of metastatic environment. This agrees with previous data that PSCA is upregulated in prostate cancer, especially in metastatic cancers. We have also generated the chimeric knockin mouse where human PSCA is expressed in place of mouse PSCA, and currently are expanding the colony.