Asano Ryutaro:Tenured Faculties|TUAT's tenure-track program

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Asano Ryutaro

Affiliation	Institute of Engineering
Division	Division of Biotechnology and Life Science
Research field	Applied bioengineering
Keyword(S)	Protein engineering, Antibody engineering, 　　　　　　　　　bispecific antibody
Url	http://web.tuat.ac.jp/~tanpaku/index.html

Research experience	･Apr.2000-Nov.2002: Research Associate, Cell Resource Center for Biomedical Research, Institute of Development, Aging, and Cancer, Tohoku University ･Dec.2002-Mar.2007: Research Associate, Department of Biomolecular Engineering, Graduate School of Engineering, Tohoku University ･Feb.2003-Mar.2005: Research Associate (concurrent post), Cell Resource Center for Biomedical Research, Institute of Development, Aging, and Cancer, Tohoku University ･Apr.2007-Dec.2010: Assistant Professor, Department of Biomolecular Engineering, Graduate School of Engineering, Tohoku University ･Jan.2011-Aug.2015: Associate Professor, Department of Biomolecular Engineering, Graduate School of Engineering, Tohoku University ･Sep.2015-Aug.2020: Associate professor, Tokyo University of Agriculture and Technology ･Sep.2020-Present: Associate Professor(Tenured), Tokyo University of Agriculture and Technology
Educational background	･Mar.1999: Bachelor of Engineering, Biomolecular Engineering, School of Engineering, Tohoku University ･Apr.1999-Mar.2000: Master Course, Graduate School of Engineering, Tohoku University ･Dec.2006: Ph.D., Graduate School of Engineering, Tohoku University
Awards	* The latest information is shown at the member's website. (At Sep. 2020) ･Mar.2009: 19th Encouragement Prize, TOKIN Science & Engineering Foundation ･Jan.2010: 15th Encouragement Prize, Aoba foundation for the promotion of engineering ･May.2011: 10th Encouragement Prize, Intelligent Cosmos Academic Foundation ･Jul.2011: Excellent Article Award of The Japanese Biochemical Society, Tohoku Branch ･Sep.2011: SUZUKI Koichi memorial award, The 84th Annual Meeting of the Japanese Biochemical Society ･May.2014: Young Investigator Award of The Japanese Biochemical Society, Tohoku Branch ･Oct.2015: The 23th Excellent Paper Award of the Society for Biotechnology, Japan ･Dec.2015: Young Investigator Award, The Japanese Biochemical Society ･Oct.2019: Top Researcher Award, Tokyo University of Agriculture and Technology
Selected papers and publications	* The latest information is shown at the member's website. (At Sep. 2020) ･Asano R., Sone Y., Makabe K., Tsumoto K., Hayashi H., Katayose Y., Unno M., Kudo T., Kumagai I., Humanization of the Bispecific Epidermal Growth Factor Receptor x CD3 Diabody and Its Efficacy as a Potential Clinical Reagent. Clin. Cancer Res., 12(13), 4036-4042 (2006) ･Asano R., Watanabe Y., Kawaguchi H., Fukazawa H., Nakanishi T., Umetsu M., Hayashi H., Katayose Y., Unno M., Kudo T., Kumagai I., Highly Effective Recombinant Format of a Humanized IgG-like Bispecific Antibody for Cancer Immunotherapy with Retargeting of Lymphocytes to Tumor Cells. J. Biol. Chem., 282(38), 27659-27665 (2007) ･Asano R., Ikoma K., Sone Y., Kawaguchi H., Taki S., Hayashi H., Nakanishi T., Umetsu M., Katayose Y., Unno M., Kudo T., Kumagai I., Highly Enhanced Cytotoxicity of a Dimeric Bispecific Diabody, the hEx3 Tetrabody. J. Biol. Chem., 285(27), 20844-20849 (2010) ･Asano R., Ikoma K., Shimomura I., Taki S., Nakanishi T., Umetsu M., Kumagai I., Cytotoxic Enhancement of a Bispecific Diabody by Format Conversion to Tandem Single-chain Variable Fragment (taFv) THE CASE OF THE hEx3 DIABODY. J. Biol. Chem., 286(3), 1812-1818 (2011) ･Asano R., Shimomura I., Konno S., Ito A., Masakari Y., Orimo R., Taki S., Arai K., Ogata H., Okada M., Furumoto S., Onitsuka M., Omasa T., Hayashi H., Katayose Y., Unno M., Kudo T., Umetsu M., Kumagai I., Rearranging the domain order of a diabody-based IgG-like bispecific antibody enhances its antitumor activity and improves its degradation resistance and pharmacokinetics. MAbs, 6(5), 1243-1254 (2014) ・Asano R., Nagai K., Makabe K., Takahashi K., Kumagai T., Kawaguchi H., Ogata H., Arai K., Umetsu M., Kumagai I. Structural considerations for functional anti-EGFR × anti-CD3 bispecific diabodies in light of domain order and binding affinity. Oncotarget, 9(17), 13884-13893 (2018) ・Asano R., Kuroki Y., Honma S., Akabane M., Watanabe S., Mayuzumi S., Hiyamuta S., Kumagai I., Sode K., Comprehensive study of domain rearrangements of single-chain bispecific antibodies to determine the best combination of configurations and microbial host cells. MAbs, 10(6), 854-863 (2018) ・Kimura H., Asano R., Tsukamoto N., Tsugawa W., Sode K., Convenient and Universal Fabrication Method for Antibody-Enzyme Complexes as Sensing Elements Using the SpyCatcher/SpyTag System. Anal. Chem., 90(24), 14500-14506 (2018)

Research Description

Although antibodies have been used as molecularly targeted agents for difficult-to-treat diseases such as cancers, the high production costs associated with mammalian expression systems continue to be a drawback. In addition, the clinical efficacy of conventional IgG antibodies is limited. I have made efforts to develop recombinant small antibodies and antitumor cytokines as novel cancer therapeutic agents, and especially focused on small bispecific antibodies, which can induce specific antitumor effects by cross-linking between cancer cells and lymphocytes, and they now attract worldwide attention. I found that a humanized small bispecific antibody (Ex3) that targets epidermal growth factor receptor (EGFR) on tumor cells and CD3 on T-lymphocytes had marked anticancer activity. Further, the function of Ex3 was enhanced by fusion with the human Fc region, multimerization, domain rearrangement, and affinity maturation; a combination of these modifications showed at least additive cytotoxic effects. Interestingly, merely rearranging the domain order of Ex3 induced substantial cytotoxic enhancements, even though the structural format remained the same. For the development of Ex3 as a novel cancer therapeutic agent, I am working to exploit an alternative host cell system and molecular modifications to facilitate purification. I also try to develop a platform for the construction of utilized biologicals and apply these techniques in biosensing field.

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About TUAT's tenure-track program

Thanks to the plentiful assigned laboratory space, start-up funds, and also clerical work support, I could move several equipments and arrange research environment without stress. I think that it is an extremely good program especially for researchers who will conduct a laboratory for the first time. In this program, the tenure posts are prepared for all researchers, thus it is expected that the research will be promoted through friendly competition, not competition for the posts. This program is also promising that interdisciplinary research will be promoted through periodic exchange meetings.

Future aspirations

One of the important mission of the Department of Technology is to produce useful things. I also have engaged in development of biologicals, especially of recombinant therapeutic antibodies based on an artificial protein design; however, the harder I studied, the more I realized it's very difficult. Now, I met the field of the biosensor. Besides addressing the study on recombinant therapeutic antibodies, I am also working to develop utilized biosensors using protein engineering.