Collaborative research aiming to develop innovative treatments over a 10-year period

T-CiRA is a joint research program by the Center for iPS Cell Research and Application (CiRA), Kyoto University and Takeda Pharmaceutical Company Limited. Over a 10-year period and under the direction of CiRA, this joint program will conduct research to develop clinical applications of iPS cells. We aim to develop innovative drugs and cell treatments in such areas as heart failure, diabetes mellitus, neuro-psychiatric disorders, cancer and intractable muscle diseases in order to fulfill the needs of patients promptly.

Professor Shinya Yamanaka

Director of Center for iPS Cell Research and Application (CiRA), Kyoto University

"This 10-year joint program with Takeda, Japan's largest pharmaceutical company, will become a powerful engine to realize medical applications using iPS cells," said Yamanaka. "We sincerely thank Takeda's commitment to iPS cell research. This partnership will contribute to the development of new therapies to cure not only major diseases but also rare ones."

Christophe Weber

Representative Director, President & CEO, Takeda

"I am excited that we will be able to collaborate with CiRA, the world's leading institute dedicated to pioneering iPS cell research," said Christophe Weber, President, and Chief Executive Officer of Takeda. "Through this partnership, our company will provide significant assistance over a long period to CiRA's research into iPS cell technology applications, which is a vital part of Japan Revitalization Strategy. It is our hope to deliver innovative treatments that meet patient needs as soon as possible through this collaboration between Takeda and CiRA."

T-CiRA (Takeda-CiRA) Joint Program Framework

T-CiRA Discovery in Takeda promotes T-CiRA Joint Program.
T-CiRA Joint Program is unique collaborations with academia and Takeda led by Professor Shinya Yamanaka in Shonan Health Innovation Park.

Yasushi Kajii

Head of T-CiRA Discovery, Takeda

In T-CiRA Joint Program takes innovative approaches toward clinical solutions for rare and intractable disease patients who were previously without effective therapeutic options. Our projects are progressing rapidly, using the power of iPS cells, to formulate novel therapeutic options. Working closely together, academic and pharma researchers are mapping uncharted territory to discover breakthrough solutions. Our approaches with iPS cells could provide transformative progress in Neuroscience, Gastroenterology, Oncology and Rare Diseases, as well as type I diabetes and heart failure, accompanied by outcomes as small molecule drugs, cell therapy and gene therapy. Our dream is that patients will receive such life-changing therapeutic options discovered through our 10-year collaborative research effort.

Takeda

• To provide collaborative funding of 20 billion yen over a 10-year period
• To provide more than 12 billion yen worth of research support
• To provide R&D know-how
• To provide research facilities at Shonan Research Center
• To provide platform for drug development
• To provide access to compound libraries
• To provide researchers

CiRA

• To direct the research program
• To provide iPS cell technologies
• To provide drug development targets and assay systems
• To provide principle investigators, researchers and postdoctoral fellows

Cutting-edge research towards the clinical application of iPS cells

Center for iPS Cell Research and Application (CiRA) will possibly bring on breakthrough changes to the future of medicine including the research and development of new drugs, cell therapies and drug safety evaluation processes. T-CiRA will conduct cutting-edge research towards the clinical application of iPS cells in areas such as heart failure, diabetes mellitus, neuro-psychiatric disorders, cancer and intractable muscle diseases at Takeda's Shonan Health Innovation Park.

Research to be conducted by T-CiRA

We are committed to providing innovative treatments to patients through iPS cell technology.

At T-CiRA, several novel research projects are underway for creating medical applications of iPSC, led by nine principal investigators.

Main Areas of Research

• Research towards the clinical application of iPS cells for heart failure, diabetes mellitus, neuro-psychiatric disorders, cancer and intractable muscle diseases, etc.
• Research to develop medicines and cell therapies using iPS cells.

Project Details

Makoto Ikeya (PI)
Daisuke Kamiya (Sub PI from CiRA)
Yayoi Toyooka (Sub PI from CiRA)
Hirokazu Matsumoto (Co PI from Takeda)
Kazumi Take (Sub PI from Takeda)

A new research platform with human iPSC-derived neural crest cells and its applications for drug discovery and regenerative medicine

Neural crest cells differentiate into diverse cell type lineages such as bones and peripheral neurons, suggesting their great potential for clinical applications. Dr. Ikeya’s team aims to create methods to maintain cultures of human iPSC-derived neural crest stem cells and to induce them to differentiate into various types of cells. Moreover, they hope to construct an disease model in combination with related technologies and apply it to drug development and regenerative medicine.

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Haruhisa Inoue (PI)
Takeshi Niki (Sub PI from CiRA)
Hiroshi Yukitake(Co-PI)
Narvaiza Inigo (Sub PI from Takeda)

ALS drug discovery and development using patient-derived iPSCs

Dr. Inoue’s team conducts research into amyotrophic lateral sclerosis (ALS), a neurodegenerative disease for which there is no effective cure. They aim to develop new therapeutic drugs using patient-derived iPSCs and Takeda's compound libraries.

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Shin Kaneko (PI)
Yuta Mishima (Sub PI from CiRA)
Shoichi Iriguchi (Sub PI from CiRA)
Akira Hayashi (Co PI from Takeda)
Yoshiaki Kassai (Co PI from Takeda)

Development of a novel immunotherapy using iPSC-derived cancer antigen-specific T-cells

Dr. Kaneko's team is trying to develop a novel cancer immunotherapy using iPSC-derived immune cells. We aspire to realize "off-the-shelf" allogeneic products for cancer patients by combining CiRA's human iPS cell stock for regenerative medicine with Takeda's experience in drug production.

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Hidetoshi Sakurai (PI)
Yuko Kokubu (Sub PI from CiRA)
Tomoya Uchimura (Sub PI from CiRA)
Ryuichi Tozawa (Co PI from Takeda)
Tomoko Nagino (Sub PI from Takeda)
Masahiro Oka (Sub PI from Takeda)

Drug discovery for intractable muscular disease using patient-derived iPSCs

Dr. Sakurai's team will create novel therapeutic drugs for intractable muscular diseases such as muscular dystrophy and investigate muscular disease models. To achieve this goal, they will utilize patient-derived iPSCs as a tool for disease modeling and drug screening.

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Tadashi Suzuki (PI)
Hiroto Hirayama (Sub PI from CiRA)
Ryuichi Tozawa (Co-PI from Takeda)
Takayuki Kamei (Sub PI from Takeda)

Development of therapeutic options for rare hereditary diseases using iPS cells

Dr. Suzuki's team is focusing on a deficiency in the NGLY1 gene that encodes for the de-N-glycosylating enzyme N-glycanase. They will develop innovative therapeutics for NGLY1 deficiency, a rare inherited disease that presently does not have any therapeutic options, through a combination of basic research findings, iPSC technology and a drug discovery platform.

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Takanori Takebe (PI)
Tadahiro Shinozawa (Co PI from Takeda)
Yasunori Nio (Sub PI from Takeda)

Miniature liver technology as a platform for research towards pharmaceutical applications

Based on human iPSC-derived miniature liver technology developed at Yokohama City University, Dr. Takebe’s team is developing a innovative system that can reproduce the complex phenomena found within patients’ bodies. This research will create a novel drug discovery system for intractable diseases and a novel predictive platform for expression analysis of rare adverse events unforeseen in traditional drug discovery research.

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Taro Toyoda (PI)
Shuhei Konagaya (Sub-PI from CiRA)
Ryo Ito (Co PI from Takeda)
Yutaka Tanoue (Sub PI from Takeda)
Hikaru Ueno (Sub PI from Takeda)
Noriko Yamazoe (Sub PI from Takeda)

iPS cell-derived pancreatic islet cell therapy for type 1 diabetes

Dr. Toyoda's team aims at developing a cell therapy product of human iPS cell-derived pancreatic islet cells encapsulated in a immuno-isolation device for severe type 1 diabetes (T1D) patients who suffer from recurrent hypoglycemia associated with a poor prognosis. Stable supply of homogenous islet cells could resolve donor shortage of pancreas/islet transplantation and provide a new treatment option for these T1D patients.

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Akitsu Hotta (PI)
Naoto Inukai (Co PI from Takeda)
Kumiko Iwabuchi (Sub PI from CiRA)
Eriya Kenjo (Sub PI from Takeda)
Hiroyuki Hozumi (Sub PI from Takeda)

Therapeutic genome editing for congenital muscular dystrophy

Dr. Hotta’s team aims to correct the causal genetic mutations involved in severe muscular dystrophy using state-of-the-art genome editing and delivery technologies. The team aims to develop proprietary technology that will enable them to create new gene therapies while, at the same time, confirming repair efficiency and safety using patient-derived iPS cells.

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Yoshinori Yoshida (PI)
Kenji Miki (Sub PI from CiRA)
Tomoyuki Nishimoto (Co PI from Takeda)
Norihisa Tamura (Sub PI from Takeda)
Yasuharu Kamachi (Sub PI from Takeda)

Development of an iPSC-based drug discovery platform and application to novel therapy for heart failure

Dr. Yoshida's team aims to create iPSC-derived cardiomyocytes suitable for regenerative therapy and drug discovery research using new technologies such as microRNA-switch technology developed at CiRA. With these cardiomyocytes, they aim to develop cell therapies against heart failure alongside next-generation drug discovery platform and new therapeutic drugs.

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Putting the promise of IPS Cells into Clinical Practice

T-CiRA Brochure

Download T-CiRA Brochure (PDF 4.42MB)

Research Achievements (as of 2019.September）

Publications

• Enhancing T Cell Receptor Stability in Rejuvenated iPSC-Derived T Cells Improves Their Use in Cancer Immunotherapy
  Atsutaka Minagawa, Toshiaki Yoshikawa, Masaki Yasukawa, Akitsu Hotta, Mihoko Kunitomo, Shoichi Iriguchi, Maiko Takiguchi, Yoshiaki Kassai, Eri Imai, Yutaka Yasui, Yohei Kawai, Rong Zhang, Yasushi Uemura, Hiroyuki Miyoshi, Mahito Nakanishi, Akira Watanabe, Akira Hayashi, Kei Kawana, Shin Kaneko
  Cell Stem Cell, 2018, vol.23, 850-858
  
  
• Phenotypic Drug Screening for Dysferlinopathy Using Patient‐Derived Induced Pluripotent Stem Cells
  Yuko Kokubu, Tomoko Nagino, Katsunori Sasa, Tatsuo Oikawa, Katsuya Miyake, Akiko Kume, Mikiko Fukuda, Hiromitsu Fuse, Ryuichi Tozawa, Hidetoshi Sakurai
  Stem Cells Translational Medicine, 2019,https://doi.org/10.1002/sctm.18-0280
  
  
• Organoid Models of Development and Disease Towards Therapy
  Yasunori Nio, Takanori Takebe
  Medical Applications of iPS Cells, Springer Nature eBOOK, 2019, 149-168
  
  
• Identification of 2,6-Disubstituted-3Η-imidazo[4,5-b]pyridines as Therapeutic Agents for Dysferlinopathies through Phenotypic Screening on Patient-Derived iPSCs
  Hiroyuki Takada, Akira Kaieda, Michiko Tawada, Tomoko Nagino, Katsunori Sasa,
  Tatsuo Oikawa, Akiko Oki, Tomoya Sameshima, Kazumasa Miyamoto, Makoto Miyamoto, Yuko Kokubu, Ryuichi Tozawa, Hidetoshi Sakurai, Bunnai Saito
  Journal of Medicinal Chemistry, in Press