Modulating Antibody Response to Cancer Self Antigen by Immunization with Various Adjuvants

초록

In order to understand the modulation of cancer progression and metastatic process by antibodies to self antigen, we designed antigenic peptide derived from PRSS14 as a tumor self antigen and tested selected antigenic peptides as preventive cancer vaccine in two mouse breast cancer models. PRSS14 (also known as epithin, ST14, and matriptase), a type II transmembrane serine protease, is an important new carcinoma marker since it plays critical roles in angiogenesis, epithelial mesenchymal transition, transendothelial migration in vitro, as well as in mouse tumor metastasis. When PRSS14 message was depleted, metastasis of 4T1 and EO771 breast cancer cells was markedly reduced in Balb/c and C57BL/6 mice, respectively. PRSS14 expressing E0771 breast cancer cells showed higher metastasis than B16 melanoma that do not express PRSS14 in C57BL/6. Antigenic peptides efficiently produced the specific antibodies of Th1 and/or Th2 with various adjuvants such as Complete Freund’s adjuvant, alum, MF59, and CpG, indicating that the responses against antitumor self antigen can be induced by breaking or escaped self-tolerance when it is conjugated. These antibodies efficiently inhibited the metastasis with two syngenic breast cancer models in antigen specific fashion since the scrambled sequence of the peptide failed to inhibit. Maintenance and control of B cell and T cell reactivity to cancer self antigen are being monitored in the cancer bearing orthotopic mouse models.