Preventive cencer vaccine strategy with antigenic peptide derived from a membrane type serine protease

초록

PRSS14/Epithin/matriptase, a type II transmembrane serine protease is upregulated in a variety of epithelial cancer cell lines and tumor tissues, and high PRSS14/Epithin level is implicated in the poor clinical outcome. We previously showed that PRSS14/Epithin/matriptase plays the critical roles in angiogenesis, epithelial mesenchymal transition, transendothelial migration in vitro, as well as tumor metastasis in vivo. In the orthotopic Balb/c breast cancer model, PRSS14 knock down of 4T1 breast cancer cell significantly increased the survival rate, decreased lung metastasis while the primary tumor growth was mildly affected. These indicated the specific roles of PRSS14/Epithin in metastasis rather than in progression of primary tumor. By immunizing with adjuvants, a designed antigenic peptide from PRSS14/Epithin/matriptase efficiently raised antigen specific TH2 type immune responses and suppressed the lung metastasis of 4T1 breast cancer. This inhibition is sequence specific since the peptide composed of scrambled sequence of the peptide failed to inhibit metastasis. Immunization of SP peptide effectively reduced lung metastasis to a degree that was similar to PRSS14 knock down in the 4T1 cancer cell. No cytotoxicity was apparent for up to 6 month with alum while some effects were detected with complete freund’s adjuvant. Therefore, it is concluded, that the selected peptide can be used as a preventive cancer metastasis vaccine without tissue damage when it is used with alum adjuvant.