Novel functional anti-HER3 monoclonal antibodies with potent anti-cancer effects on various human epithelial cancers

Resistance of progressive cancers against chemotherapy is a serious clinical problem. In this context, human epidermal growth factor receptor 3 (HER3) can play important roles in drug resistance to HER1- and HER2- targeted therapies. Since clinical testing of anti-HER3 monoclonal antibodies (mAbs) such as patritumab could not show remarkable effect compared with existing drugs, we generated novel mAbs against anti-HER3. Novel rat mAbs reacted with HEK293 cells expressing HER3, but not with cells expressing HER1, HER2 or HER4. Specificity of mAbs was substantiated by the loss of mAb binding with knockdown by siRNA and knockout of CRISPR/Cas9-based genome-editing. Analyses of CDR sequence and germline segment have revealed that seven mAbs are classified to four groups, and the binding of patritumab was inhibited by one of seven mAbs. Seven mAbs have shown reactivity with various human epithelial cancer cells, strong internalization activity of cell-surface HER3, and inhibition of NRG1 binding, NRG1-dependent HER3 phosphorylation and cell growth. Anti-HER3 mAbs were also reactive with in vivo tumor tissues and cancer tissue-originated spheroid. Ab4 inhibited in vivo tumor growth of human colon cancer cells in nude mice. Present mAbs may be superior to existing anti-HER3 mAbs and support existing anti-cancer therapeutic mAbs

The Development and Assessment on the Social Studies Handbook for Supporting Teacher’s Lesson Planning and Improvement : A Content Structure of Handbook which can be Applied to Pre-service and In-service Teacher Education

The purposes of this paper are to develop the draft of handbook for planning, teaching and accessing the class of social studies and evaluate effects of the handbook for teacher training and their professional development. The structure of the first draft was designed based on Kolb’s learning theory. The present results suggested that the usefulness of the contents structure was perceived by (1) pre-service teachers and (2) in-service teachers, and the possibility for application was also recognized by the teacher educator as (3) university professor who teach methods courses, (4) senior supervisor who is in charge of designing the professional development programs and (5) younger supervisor who is in charge of tutoring the novice teacher, but they illustrated their different types of the significances, limits and utilization according to their purposes and as well as their responsibility. The authors implicated the alterative design of the handbook based on Korthagen’s reflective learning model for meeting their purposes and solving the structural problems inherit in the handbook