Laboratory of Advanced Biopharmaceuticals (This laboratory is run in a joint program by NIBIOHN and Kyoto University.)

1. Members

2. Background and objectives

Diversity in drug modalities is important as the application of pharmaceuticals is broadened. This laboratory contributes to development of new technologies in new biopharmaceutical modalities including engineered antibodies and their drug conjugates.

3. Research

We design functions of biparatopic antibodies by comprehensive epitope selection (Figure). New technologies are also developed to go beyond conventional antibody drugs by utilizing the technologies of protein engineering and synthetic chemistry.

4. Link

Our research activity is also conducted in Laboratory of Biopharmaceutical Chemistry, Graduate School of Pharmaceutical Sciences, Kyoto University.

http://www.pharm.kyoto-u.ac.jp/kunib/en/biopharm/index.html

5. Reference

1. Osawa T, Kita R, Kasahara Y, Yamaguma H, Nakayama T, Kamada H, Obika S.  In vitro screening of chemically synthesized dipeptide-antisense oligonucleotide conjugates to identify ligand molecules enhancing their activity Bioorg Med Chem. 22024 Aug 1:110:117814. doi: 10.1016/j.bmc.2024.117814.
2. Inoue M, Tsuji Y, Kashiwada A, Yokoyama A, Iwata A, Abe Y, Kamada H, Tsunoda SI. An immunocytokine consisting of a TNFR2 agonist and TNFR2 scFv enhances the expansion of regulatory T cells through TNFR2 clustering, Biochem Biophys Res Commun. 2024 Feb 19:697:149498. doi: 10.1016/j.bbrc.2024.149498.
3. Nishiyama K, Akiba H, Nagata S, Tsumoto K, Kamada H, Ohno H. A Proximity-Induced Fluorogenic Reaction Triggered by Antibody-Antigen Interactions with Adjacent Epitopes. Angew Chem Int Ed Engl. 2023 Jul 24;62(30):e202306431. doi: 10.1002/anie.202306431.
4. Inoue M, Tsuji Y, Ueno R, Miyamoto D, Tanaka K, Moriyasu Y, Shibata S, Okuda M, Ando D, Abe Y, Kamada H, Tsunoda SI. Bivalent structure of a TNFR2-selective and agonistic TNF-α mutein Fc-fusion protein enhances the expansion activity of regulatory T cells. Sci Rep. 2023 Aug 23;13(1):13762. doi: 10.1038/s41598-023-40925-9.
5. Akiba H, Fujita J, Ise T, Nishiyama K, Miyata T, Kato T, Namba K, Ohno H, Kamada H, Nagata S, Tsumoto K. Development of a 1:1-binding biparatopic anti-TNFR2 antagonist by reducing signaling activity through epitope selection. Commun Biol. 2023 Sep 27;6(1):987. doi: 10.1038/s42003-023-05326-8.
6. Suzuki K, Tajima M, Tokumaru Y, Oshiro Y, Nagata S, Kamada H, Kihara M, Nakano K, Honjo T, Ohta A., Anti-PD-1 antibodies recognizing the membrane-proximal region are PD-1 agonists that can down-regulate inflammatory diseases. Sci Immunol. 8(79): eadd4947. DOI: 10.1126/sciimmunol.add4947. (2023)
7. Inoue M, Tsuji Y, Ueno R, Miyamoto D, Tanaka K, Moriyasu Y, Shibata S, Okuda M, Ando D, Abe Y, Kamada H, Tsunoda SI., Bivalent structure of a TNFR2-selective and agonistic TNF-α mutein Fc-fusion protein enhances the expansion activity of regulatory T cells. Sci Rep. 13(1):13762. DOI: 10.1038/s41598-023-40925-9. (2023)
8. Yamaguchi T, Hoshizaki M, Minato T, Nirasawa S, Asaka MN, Niiyama M, Imai M, Uda A, Chan JF, Takahashi S, An J, Saku A, Nukiwa R, Utsumi D, Kiso M, Yasuhara A, Poon VK, Chan CC, Fujino Y, Motoyama S, Nagata S, Penninger JM, Kamada H, Yuen KY, Kamitani W, Maeda K, Kawaoka Y, Yasutomi Y, Imai Y, Kuba K., ACE2-like carboxypeptidase B38-CAP protects from SARS-CoV-2-induced lung injury. Nat Commun. 12:6791. doi: 10.1038/s41467-021-27097-8. (2021)
9. Urano E, Okamura T, Ono C, Ueno S, Nagata S, Kamada H, Higuchi M, Furukawa M, Kamitani W, Matsuura Y, Kawaoka Y, Yasutomi Y. COVID-19 cynomolgus macaque model reflecting human COVID-19 pathological conditions.　Proc Natl Acad Sci U S A. 118:e2104847118. DOI: 10.1073/pnas.2104847118. (2021)
10. Asaka MN, Utsumi D, Kamada H, Nagata S, Nakachi Y, Yamaguchi T, Kawaoka Y, Kuba K, Yasutomi Y., Highly susceptible SARS-CoV-2 model in CAG promoter–driven hACE2-transgenic mice.　JCI　Insight.;6:e152529. DOI: 10.1172/jci.insight.152529. (2021)
11. Akiba H, Ise T, Nagata S, Kamada H, Ohno H, Tsumoto K., Production of IgG1-based bispecific antibody without extra cysteine residue via intein-mediated protein trans-splicing, Sci. Rep. 11, 19411. DOI:10.1038/s41598-021-98855-3 (2021)

Laboratory of Advanced Biopharmaceuticals