Browse

Targeting metastatic breast cancer with peptide epitopes derived from autocatalytic loop of Prss14/ST14 membrane serine protease and with monoclonal antibodies

Cited 2 time in Web of Science Cited 2 time in Scopus
Authors
Kim, Ki Yeon; Yoon, Minsang; Cho, Youngkyung; Lee, Kwang-Hoon; Park, Sora; Lee, Se-ra; Choi, So-Young; Lee, Deokjae; Yang, Chansik; Cho, Eun Hye; Jeon, Sangjun Davie; Kim, Seok-Hyung; Kim, Chungho; Kim, Moon Gyo
Issue Date
2019-08-19
Publisher
BioMed Central
Citation
Journal of Experimental & Clinical Cancer Research, 38(1):363
Keywords
Prss14MetastasisImmunotherapyCancer vaccineAutocatalytic loop
Abstract
Background
In order to develop a new immunotherapeutic agent targeting metastatic breast cancers, we chose to utilize autocatalytic feature of the membrane serine protease Prss14/ST14, a specific prognosis marker for ER negative breast cancer as a target molecule.

Methods
The study was conducted using three mouse breast cancer models, 4 T1 and E0771 mouse breast cancer cells into their syngeneic hosts, and an MMTV-PyMT transgenic mouse strain was used. Prss14/ST14 knockdown cells were used to test function in tumor growth and metastasis, peptides derived from the autocatalytic loop for activation were tested as preventive metastasis vaccine, and monoclonal and humanized antibodies to the same epitope were tested as new therapeutic candidates. ELISA, immunoprecipitation, Immunofluorescent staining, and flow cytometry were used to examine antigen binding. The functions of antibodies were tested in vitro for cell migration and in vivo for tumor growth and metastasis.

Results
Prss14/ST14 is critically involved in the metastasis of breast cancer and poor survival rather than primary tumor growth in two mouse models. The epitopes derived from the specific autocatalytic loop region of Prss14/ST14, based on structural modeling acted as efficient preventive metastasis vaccines in mice. A new specific monoclonal antibody mAb3F3 generated against the engineered loop structure could reduce cell migration, eliminate metastasis in PyMT mice, and can detect the Prss14/ST14 protein expressed in various human cancer cells. Humanized antibody huAb3F3 maintained the specificity and reduced the migration of human breast cancer cells in vitro.

Conclusion
Our study demonstrates that Prss14/ST14 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.
ISSN
1756-9966
Language
English
URI
http://hdl.handle.net/10371/162625
DOI
https://doi.org/10.1186/s13046-019-1373-y
Files in This Item:
Appears in Collections:
College of Natural Sciences (자연과학대학)Dept. of Biological Sciences (생명과학부)Journal Papers (저널논문_생명과학부)
  • mendeley

Items in S-Space are protected by copyright, with all rights reserved, unless otherwise indicated.

Browse