Adjuvant Selection is Critical for the Preventive Cancer Vaccine with PRSS14/Epithin Peptide Antigen against Metastatic Breast Cancer

초록

Antigenic cancer vaccine against metastastic breast cancer can be useful strategy to enhance survival of breast cancer patients when popular therapeutic antibody is not available. Previously we showed PRSS14/Epithin is a critical parameter and a useful therapeutic target for human triple negative breast cancer using TCGA breast cancer database. We also showed it plays important roles in EMT, angiogenesis, transendothelial cell migration. 4T1 and E0771 mouse breast cancer cells show PRSS14/Epithin dependent tumor growth and lung metastasis when they are orthotopically injected into the syngenic mice. When several peptides derived from PRSS14/Epithin were immunized, they effectively reduce primary tumor size and metastasis of 4T1 and E0771 in sequence specific fashion. Host mice produced sequence specific antibodies of both TH1 and/or TH2 types depending on adjuvants. A transgenic mouse model that develops spontaneous breast cancer, MMTV-PyMT, was tested for the metastasis vaccine with two different adjuvants, CFA/IFA and Alum. Interestingly, MMTV-PyMT mice showed reduced tumor growth and metastasis only with CFA/IFA, but showed adverse endpoints with Alum adjuvant, indicating that the host basal TH- types are critical for the vaccine effect against metastatic breast cancer. Among the immune cell populations in the tumor tissues, CD11b+F4/80+Gr1-SSChigh eosinophils and CD11b+F4/80+Gr1int monocytes showed strong correlation with positive vaccine effects. Therefore, host innate immune system significantly contributes in managing breast cancer in addition to Ag specific response. Key words: Breast cancer metastasis, PRSS14/Epithin, Metastasis vaccine, Adjuvant, Immune response type