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International Vaccine Design Center

Division of Human Immunology(Human Immune-Profiling Team)

ヒト免疫プロファイリング系 ヒト免疫学分野
Professor
Ken Ishii, M.D., Ph.D.
Visiting Professor
Noriko Toyama-Sorimachi, Ph.D.
Project Associate Professor Toshihiko Kobayashi, Ph.D.

教 授
客員教授
特任講師

医学博士
博士（医学）
博士（医学）

石
反
小

井
町
林

典
俊

健
子
彦

The laboratory is consisted of two groups working on vaccine and immunometabolism
lead by Ken Ishii and Noriko Toyama-Sorimachi, respectively to conduct novel
research on vaccine immunology and immunometabolism towards human immuneprofiling to understand why and how our immune system respond to infection andother immunological disorders.

1.  Establishment of a platform for rapid development of vaccines and therapeutics in the eventof an infectious disease pandemic.
Background: After the experience of the COVID-19 pandemic, various research systems for infectious disease pandemics have been in place aroundthe world. IMSUT is the central hub of SCARDA, andthe University of Tokyo has set up UTOPIA, where
researchers have begun to work together. However,much work remains to be done to overcome the various obstacles that may arise during a disaster. To address issues such as how to rapidly obtain researchmaterials including purified proteins as antigens andantibodies as reagents to test vaccine efficacy, andhow to rapidly prepare various tools and technologies for therapeutic drug discovery in parallel withvaccine development, further collaboration among
researchers across disciplines, organizations, and institutions, which is unique to emergency situations, isessential. Dr. Sorimachi of the International Vaccine
Design Center is the program officer in the BINDS
project of AMED. BINDS is a platform consisting of agroup of academic researchers with world-class ana-

lytical technologies and supports academic drug discovery research with advanced technologies ranging
from structural analysis, hit discovery, protein expression analysis, and various omics analyses to insilico drug discovery.
Methods: In response to the spread of M-pox, we
worked on an interproject collaboration between
SCARDA and BINDS, using the SCARDA Ishii team’s
project to test smallpox vaccine efficacy against M-pox
as a practical problem. In addition, the BINDS platform has begun to centralize plasmid information to
expedite the process of applying for recombinant
DNA experiments.
Conclusions: The collaboration between the
SCARDA Ishii team and the BINDS researchers has
enabled rapid progress in the immunological analysisof the effects of smallpox vaccine. This successful caseis the first inter-project collaboration within AMED,
and demonstrates that cooperation between SCARDA and BINDS can create a strong research impetus
in times of emergency. We will continue to work on
the establishment of a system of research collaboration to address specific issues anticipated in an emergency. Collaboration with other researchers on hu-

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man immunology using human samples and celllines are underway and some of them have resulted in
the publications in 2023.
2.  Initiatives to out-license lead compounds to
a company for the development of therapeutic
agents for autoimmune diseases.
We have been conducting exploratory drug discovery research to develop novel therapeutics for autoimmune diseases by targeting amino acid transporters that are preferentially expressed in immune
cells, and has succeeded in obtaining lead compounds
that suppress inflammatory cytokine and type I inter-

feron production at sub-μM levels. Since a foreign
pharmaceutical company have been expressing
strong interest in our lead compounds, we had ongoing meetings under a confidentiality agreement regarding licensing negotiations and a third-party evaluation of the compound’s potential. This was followedby discussions on the content of a term sheet forout-licensing and an agreement was reached. We arein the process of drafting an agreement. We expect tobe able to out-license the compounds in 2024. In parallel, with the same pharmaceutical company, we
have been preparing to enter into a broad joint research agreement.

Publication
1.		Kobayashi T. and Toyama-Sorimachi N. Metabolic control from the endolysosome: lysosome-resident amino acid transporters open novel therapeutic possibilities. Front. Immunol. 2023 14:1243104. doi:10.3389/fimmu.2023.1243104.
2.		Palacpac NMQ, Ishii KJ, Arisue N, Tougan T, Horii
T. Immune tolerance caused by repeated P. falciparum infection against SE36 malaria vaccine candidate antigen and the resulting limited polymorphism. Parasitol Int. 2024 Apr;99:102845. doi:
10.1016/j.parint.2023.102845.
3.		
Ouédraogo A, Bougouma EC, Palacpac NMQ,
Houard S, Nebie I, Sawadogo J, Berges GD, Soulama I, Diarra A, Hien D, Ouedraogo AZ, KonatéAT, Kouanda S, Myoui A, Ezoe S, Ishii KJ, Sato T,
D’Alessio F, Leroy O, Tiono AB, Cousens S, Horii
T, Sirima SB. Safety and immunogenicity of BKSE36/CpG malaria vaccine in healthy Burkinabe
adults and children: a phase 1b randomised, controlled, double-blinded, age de-escalation trial.
Front Immunol. 2023 Oct 16;14:1267372. doi: 10.
3389/fimmu.2023.1267372.
4.		Yao L, Chemaitelly H, Goldman E, Gudina EK,
Khalil A, Ahmed R, James AB, Roca A, Fallah MP,
Macnab A, Cho WC, Eikelboom J, Qamar FN,
Kremsner P, Oliu-Barton M, Sisa I, Tadesse BT,
Marks F, Wang L, Kim JH, Meng X, Wang Y, Fly
AD, Wang CY, Day SW, Howard SC, Graff JC,
Maida M, Ray K, Franco-Paredes C, Mashe T,
Ngongo N, Kaseya J, Ndembi N, Hu Y, Bottazzi
ME, Hotez PJ, Ishii KJ, Wang G, Sun D, Aleya L,
Gu W. Time to establish an international vaccine
candidate pool for potential highly infectious respiratory disease: a community’s view. EClinicalMedicine. 2023 Sep 26;64:102222. doi: 10.1016/j.
eclinm.2023.102222.
5.		Dzau V, Swaminathan S, Baker C, Bright RA, Castillo J, Chuan TC, Draghia-Akli R, Eardley-Patel R,
Gao GF, Ishii K, Tebeje YK, Lambe T, Machingaidze S, Røttingen JA, Shaligram U, Simão M,
Swarup R, Toussaint JF, Wairagkar NS. The 100

Days Mission: how a new medical-countermeasures network can deliver equity and innovation.
Lancet. 2023 Oct 28;402(10412):1507-1510. doi:
10.1016/S0140-6736(23)01775-0.
6.		Katsikis PD, Ishii KJ, Schliehe C. Challenges in developing personalized neoantigen cancer vaccines. Nat Rev Immunol. 2023 Oct 2. doi: 10.1038/
s41577-023-00937-y.
7.		Konaka H, Kato Y, Hirano T, Tsujimoto K, Park J,
Koba T, Aoki W, Matsuzaki Y, Taki M, Koyama S,
Itotagawa E, Jo T, Hirayama T, Kawai T, Ishii KJ,
Ueda M, Yamaguchi S, Akira S, Morita T, Maeda
Y, Nishide M, Nishida S, Shima Y, Narazaki M,
Takamatsu H, Kumanogoh A. Secretion of mitochondrial DNA via exosomes promotes inflammation in Behçet’s syndrome. EMBO J. 2023 Oct
16;42(20):e112573. doi: 10.15252/embj.2022112573.
8.		Toriyama M, Rizaldy D, Nakamura M, Atsumi Y,
Toriyama M, Fujita F, Okada F, Morita A, Itoh H,
Ishii KJ. Dendritic cell proliferation by primarycilium in atopic dermatitis. Front Mol Biosci.
2023 Apr 26;10:1149828. doi: 10.3389/fmolb.2023.
1149828.
9.		Otsuka Saito K, Fujita F, Toriyama M, Utami RA,
Guo Z, Murakami M, Kato H, Suzuki Y, Okada F,
Tominaga M, Ishii KJ. Roles of TRPM4 in immune
responses in keratinocytes and identification of anovel TRPM4-activating agent. Biochem Biophys
Res Commun. 2023 Apr 30;654:1-9. doi: 10.1016/j.
bbrc.2023.02.062
10.	Atsumi Y, Toriyama M, Kato H, Nakamura M,
Morita A, Takaishi M, Saito K, Tanaka M, Okada F,
Tominaga M, Ishii KJ, Fujita F. Anti-Inflammatory
Role of TRPV4 in Human Macrophages. Immunohorizons. 2023 Jan 1;7(1):81-96. doi: 10.4049/immunohorizons.2200100.
PCT application
1.		
WO2023/008402 A1: THERAPEUTIC AGENT
FOR PULMONARY FIBROSIS

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2.		WO2023/008451 A1: TREATMENT AND REHABILITATION METHOD FOR PULMONARY FIBROSIS.