M.D., Ph.D. Professor Shin Kaneko
In the laboratory of regenerative immunotherapy, we are conducting research on immune cell regeneration from iPSC and its clinical application. Individual research themes for researchers and students include establishment of iPS cells and differentiation of various types of immune cell, enhancement of immune cell function and immunogenicity control mainly by gene modification. As clinical development, we are conducting research on optimization of immune cell manufacturing process, clinical trials aimed at establishing new treatment, and reverse translational research using clinical trial samples.
Research and Education
T cells are immune cells that recognize target cells in an antigen-specific manner and exert their functions. We previously found that T cell receptor (TCR) gene sequence of the original T cell is preserved in the iPS cell (T-iPS cell) that is obtained by reprogramming of the T cell. Using this feature, we have established a method for inducing a large amount of rejuvenated antigen-specific T cells from antigen-specific human T-iPS cells. We also showed that by introducing a disease-specific TCR gene into HLA homodonor-derived iPS cells, antigen-specific T cells that can be used in multiple patients can be produced. In addition, we have shown that a small number of iPS cells can provide a wide range of therapeutic T cells by reducing the immunogenicity of iPS cells using multiple gene editing methods. Some of these technologies have been out-licensed and clinical development is progressing.
- Wang B, Iriguchi S, Waseda M, Ueda N, Ueda T, Xu H, Minagawa A, Ishikawa A, Yano H, Ishi T, Ito R, Goto M, Takahashi R, Uemura Y, Hotta A, Kaneko S. Generation of hypoimmunogenic T cells from genetically engineered allogeneic human induced pluripotent stem cells. Nature Biomedical Engineering 5:429-440, 2021
- Iriguchi S, Yasui Y, Kawai Y, Arima S, Kunitomo M, Sato T, Ueda T, Minagawa A, Mishima Y, Yanagawa N, Baba Y, Miyake Y, Nakayama K, Takiguchi M, Shinohara T, Nakatsura T, Yasukawa M, Kassai Y, Hayashi A, Kaneko S. A clinically applicable and scalable method to regenerate T-cells from iPSCs for off-the-shelf T-cell immunotherapy. Nature Communications 2021(12), 2021
- Xu H, Wang B, Ono M, Kagita A, Fujii K, Sasakawa N, Ueda T, Gee P, Nishikawa M, Nomura M, Kitaoka F, Takahashi T, Okita K, Yoshida Y, Kaneko S, Hotta A. Targeted Disruption of HLA Genes via CRISPR-Cas9 Generates iPSCs with Enhanced Immune Compatibility. Cell Stem Cell, 24(4):566-578.e7, 2019
- Minagawa A, Yoshikawa T, Yasukawa M, Hotta A, Kunitomo M, Iriguchi S, Takiguchi M, Kassai Y, Imai E, Yasui Y, Kawai Y, Zhang R, Uemura Y, Miyoshi H, Nakanishi M, Watanabe A, Hayashi A, Kawana Kei, Fujii T, Nakatsura T, Kaneko S. Enhancing T cell Receptor Stability in Rejuvenated iPSC-derived T cells improves their use in cancer immunotherapy. Cell Stem Cell, 23(6):850-858.e4 1-9, 2018
- Nishimura T, Kaneko S, Kawana-Tachikawa A, Tajima Y, Gotoh H, Zhu D, Nakayama K, Iriguchi S, Uemura Y, Shimizu T, Takayama N, Yamada D, Nishimura K, Ohtaka M, Watanabe N, Takahashi S, Iwamoto A, Koseki H, Nakanishi M, Eto K, Nakauchi H. Generation of rejuvenated antigen-specific T cells by reprogramming to pluripotency and redifferentiation. Cell Stem Cell, 12(1):114-126, 2013
Professor: Shin Kaneko