DEVELOPMENT OF ANTI APOPTOTIC DNA VACCINE BASED IMMUNTERAPY MODEL AGAINST BREAST CANCER
Project no. 63 · Status: Kapanmış · 2016
Summary
Breast cancer, which is the most common cancer type in women in the world, is an important cause of death today. Human epidermal growth factor receptor 2 (Her2) overexpression associated with poor prognosis in breast cancer occurs in 20-30% of patients. Today, although the survival rate of Her2 positive breast cancer patients treated with monoclonal antibodies is increased, patients gain resistance to full-length Her2 targeted therapies over time. The aim of this project is to develop a DNA vaccine that expresses an innovative Her2 protein, which includes immunogenic epitopes of Her2 protein, and to stimulate a strong immune response. For this purpose, an innovative Her2 molecule including all immunogenic epitopes was designed by examining the extracellular domain of Her2 by bioinformatics methods. Then, the in vitro expression level as well as immune response stimulated by DNA vaccine expressing this innovative multiepitop Her2 molecule in in vivo mouse model was investigated by ELISA and Western blot methods. According to the in vitro expression results, it was observed that DNA vaccine synthesized recombinant protein with a molecular weight of ~45 kDa recombinant protein. Moreover, DNA vaccine significantly increased total IgG response in mice (P <0.01). When the secreted IFN-? and IL-4 responses are examined in addition to the IgG1 and IgG2a response, it was shown that a balanced Th1-Th2 immune response was achieved. In the light of these results, strong humoral and cellular immune response induced by DNA vaccine can be protective against Her2 receptor positive breast cancer.