1. Members

Project leader	KAMADA Haruhiko
Project Researcher	NAKAYAMA Taisuke
Research Fellow	NIIYAMA Nayumi
Technical assistant	TAKESHIMA Madoka, YAMANAKA Yuko, OKABE Akiko
Administrative Assistant	KATORI Miho

2. Background and objectives

Recently, the number of clinically available biopharmaceuticals such as antibodies, cytokines, peptides is rapidly increasing. These biopharmaceuticals have caused a paradigm shift in disease treatment and has led to an improvement in the quality of life of patients with refractory cancers and autoimmune diseases. However, the technology for biopharmaceutical development is not well established. Indeed, an efficient technology for developing biopharmaceuticals is urgently required. In this regard, our project focuses on developing new technologies with a particular emphasis on the phage display system, which can generate a large repertoire of antibodies or mutant proteins. Our research project also includes proteomics-based studies for the identification of novel diagnostic markers and drug targets of refractory diseases. We are also interested in the development of novel drug delivery systems, such as nanotechnology-based devices or synthetic polymer-based devices, for controlling the in vivo behavior of biopharmaceuticals.

3. Overview of our research

3-1．Development of biopharmaceuticals and elucidation of molecular mechanisms for intractable diseases using antibody proteomics technology

Recently, a large number of disease-related proteins have been identified by genome or proteome analysis. However, discovery of useful biomarkers for drug development has been limited. One reason is the difficulty of efficiently selecting potential biomarkers from among the many candidate proteins. To overcome this problem, we have recently developed "antibody proteomics technology", which integrates phage antibody library technology with proteomics and tissue microarray technology. This technology can be used to discover biomarker proteins from complex samples (e.g., cell lysate or tissue homogenate) by isolating antibodies against each promising biomarker molecule in a rapid and comprehensive manner. Such an approach enables the elucidation of molecular pathogenesis of refractory diseases as well as the development of diagnostic products or therapeutic agents.

3-2．Development of technology for creating functional protein drugs to treat refractory diseases

Although biopharmaceuticals have high therapeutic potency, they have common problems such as unexpected side-effects and reduced pharmacological effect after frequent administration. Our project aims to overcome these problems by developing the following new technologies. (I) Development of a rapid system to create functional mutant proteins with high receptor subtype specificity or clinical applicability using a phage display technique. (II) Establishment of a novel drug delivery system to improve in vivo stability and target selectivity of biopharmaceuticals. (III) Development of technology for structural analysis using nuclear magnetic resonance (NMR) and mass spectrometry (MS). We are currently attempting to integrate these approaches to create effective and safe biopharmaceuticals for the application of immunomodulating therapy against intractable diseases, such as autoimmune disorders.

Laboratory of Biopharmaceutical Research

Website	https://www.nibiohn.go.jp/bio-r/
E-mail	kamada*nibiohn.go.jp (replace * by @)