Anticancer Approaches with Peptide Epitopes derived from and with Monoclonal Antibodies against Autocatalytic Loop of Prss14 /epithin

초록

In order to develop new immunotherapeutic agents targeting metastatic breast cancers, we chose to utilize autocatalytic feature of the membrane serine protease Prss14/epithin, a specific prognosis marker for ER negative breast cancer as a target molecule. Prss14/epithin is critically involved in the metastasis of breast cancer and poor survival rather than primary tumor growth in two mouse models (4T1 and E0771 mouse breast cancer cells into their syngeneic hosts). The epitopes derived from the specific autocatalytic loop region of Prss14/epithin, designed based on structural modeling, acted as efficient preventive metastasis vaccines in three mouse models. A new specific monoclonal antibody mAb3F3 generated against the engineered loop structure specifically binds to the epitope, and could reduce cell migration, eliminate metastasis in PyMT mice, and can detect the Prss14/epithin protein expressed in various human cancer cells. Humanized antibody huAb3F3 maintained the specificity and reduced the migration of human breast cancer cells in vitro. Our study demonstrates that Prss14/epithin is an important target for modulating metastasis. Our newly developed hybridoma mAbs and humanized antibody can be further developed as new promising candidates for the use in diagnosis and in immunotherapy of human metastatic breast cancer.