Build-up functionalization of anti-EGFR × anti-CD3 bispecific diabodies by integrating high-affinity mutants and functional molecular formats

Designing non-natural antibody formats is a practical method for developing highly functional next-generation antibody drugs, particularly for improving the therapeutic efficacy of cancer treatments. One approach is constructing bispecific antibodies (bsAbs). We previously reported a functional humanized bispecific diabody (bsDb) that targeted epidermal growth factor receptor and CD3 (hEx3-Db). We enhanced its cytotoxicity by constructing an Fc fusion protein and rearranging order of the V domain. In this study, we created an additional functional bsAb, by integrating the molecular formats of bsAb and high-affinity mutants previously isolated by phage display in the form of Fv. Introducing the high-affinity mutations into bsDbs successfully increased their affinities and enhanced their cytotoxicity in vitro and in vivo. However, there were some limitations to affinity maturation of bsDb by integrating high-affinity Fv mutants, particularly in Fc-fused bsDb with intrinsic high affinity, because of their bivalency. The tetramers fractionated from the bsDb mutant exhibited the highest in vitro growth inhibition among the small bsAbs and was comparable to the in vivo anti-tumor effects of Fc-fused bsDbs. This molecule shows cost-efficient bacterial production and high therapeutic potential

Transformation of the Higher Education Policy-making Process in the 2010s: From Ministry-led to Executive-led Higher Education Policy

This book is composed of the results of the Higher Education Policy Research Project of the Japanese Association of Higher Education Research, which was proposed by the President of the Association, Masayuki Kobayashi, and was carried out by a group of researchers within the association under the leadership of board member Takashi HATA. Research on higher education policy-making has been one of the major topics of interest since the establishment of the Association. Indeed, the association’s mission statement declares, “the establishment of an academic society is becoming an ever more critical issue for promoting cooperation and exchanges among the researchers from different study fields, strengthening the theoretical and methodological basis of research, seeking further deepened and developed research, dissemination of the outcomes of this research and contribution to the solution of practical and policy-related challenges.” This research project aims to study the process of policy-making for higher education in Japan, which has changed rapidly in recent years. This change is occurring not only in Japan but also in Europe and the United States. In order to study from a global perspective, the research project was carried out with the participation of experts studying higher education in the United States, France, and the United Kingdom, and new research results were produced through comparative higher education policy analysis. In the Higher Education Policy Project, members interviewed officials from the Ministry of Education, Culture, Sports, Science and Technology (MEXT), and have been energetically studying the policy-making process, especially the relationship between the official residence and the MEXT. At the same time, they have analyzed the decision-making process of higher education policies in each country. We believe that research that examines the decision-making process of higher education policies in so many countries is unparalleled and offers an unprecedented contribution to higher education research.はじめに… 小林雅之 1 序章　高等教育政策決定過程の変容を探求する－研究の課題… 羽田貴史 3 第1章　2010年代高等教育政策決定過程の変容… 羽田貴史 9 第2章　高等教育政策にかかわる会議体とアクター… 丸山和昭 33 第3章　「高等教育の修学支援新制度」の形成過程－政治と官邸主導による新制度創設… 白川優治 51 第4章　高大接続改革への疑義… 荒井克弘 65 第5章　アメリカの高等教育政策決定過程と大統領府… 塙武郎 83 第6章　フランスの高等教育政策決定過程… 大場淳 97 第7章　イギリスの高等教育政策決定過程と首相官邸－証拠に基づく政策形成（EBPM）の仕組み… 田中正弘 109 おわりに… 羽田貴史 12