Hiroshi Kawamoto,
Professor, Laboratory of Immunology, Institute for Frontier Life and Medical Sciences,
Kyoto University
Hiroshi Kawamoto is a Professor of Laboratory of Immunology at Institute for Frontier Life and Medical Sciences (IFLMS), Kyoto University, serving also as the Deputy Director of IFLMS. He is working on the basic research that aims to clarify molecular mechanisms of lineage commitment in early hematopoiesis/lymphopoiesis, as well as on the study for the development of immune cell therapy using T cells regenerated from ES/iPS cells. He graduated from Faculty of Medicine, Kyoto University in 1986, and worked as a physician in hospital for three years. He took his doctor course in Hematology Department of Kyoto University from 1989, and then joined Prof. Katsura’s laboratory in Chest Disease Institute (currently IFLMS) from 1994 to 2001 as a visiting researcher, where he started to study the early hematopoiesis and T cell development. In 2001, He became an assistant professor of Prof. Minato’s laboratory in Faculty of Medicine, Kyoto University. He was then promoted to be a team leader of RIKEN Research Center for Allergy and Immunology, Yokohama, in 2002. In RIKEN, in parallel with the basic research, he has started the study on regenerative medicine. He moved to Kyoto University in 2012.
Generation of CTLs from iPSCs Transduced with TCR Genes: Toward the Development of “Off-the-Shelf T Cells”
Tuesday, 12 November 2019 at 14:30
Add to Calendar ▼2019-11-12 14:30:002019-11-12 15:30:00Europe/LondonGeneration of CTLs from iPSCs Transduced with TCR Genes: Toward the Development of “Off-the-Shelf T Cells”Cell and Gene Therapy Asia 2019 in Kobe, JapanKobe, JapanSELECTBIOenquiries@selectbiosciences.com
We have proposed a strategy to use iPSC technology for expansion of tumor antigen specific CTLs; iPSCs produced from T cells (T-iPSCs) inherit rearranged TCR genes, and thus all regenerated T cells from T-iPSCs express the same TCR. Based on this idea, we have succeeded in regenerating MART1-specific CTLs from a melanoma patient (Vizcardo et al, Cell Stem Cell, 2013). Recently we have developed a culture method by which CTLs expressing CD8alpha-beta heterodimer with high antigen specific cytotoxicity can be regenerated.
To apply this approach in allogeneic setting, we thought of a method in which non-T cell derived iPSCs are transduced with exogenous TCR genes (TCR-iPSCs). As a source of iPSCs, we decided to use HLA-haplotype homo iPSCs; regenerated cells from such iPSCs could be transplanted to HLA-hetero recipients. At present, top three frequent HLA-homo iPSC lines are available, covering 30% of the Japanese population. To test the idea of TCR-iPSCs, we lentivirally transduced non-T cell derived iPSCs with WT1-specific TCR gene cloned by our group from CTLs regenerated from WT1-T-iPSCs, which had originally been established from WT1-specific CTLs expanded from peripheral T cells of a healthy volunteer. Regenerated CTLs from TCR-iPSCs were found to exhibit cytotoxicity comparable to those from T-iPSCs carrying the same WT1-TCR, indicating that this strategy works well.
We applied this system to the TCRs that have been used in clinical trials in Japan. We transduced HLA-homo iPSCs with WT1-specific TCR that has been used in clinical trial of TCR gene transfer therapy against leukemia (Ehime University). Regenerated CTLs from WT1-TCR-iPSCs suppressed growth of WT1-expressing renal cell carcinoma cells in patient-derived xenograft model. We also applied this system to NY-ESO1-TCR that has been used in clinical trial targeting synovial sarcoma or melanoma (Mie University). Regenerated NY-ESO1-CTLs showed cytotoxicity against myeloma cells in xenograft model. These results collectively demonstrate the feasibility of the TCR-iPSC strategy against various types of cancer, including solid tumor.
Add to Calendar ▼2019-11-11 00:00:002019-11-12 00:00:00Europe/LondonCell and Gene Therapy Asia 2019Cell and Gene Therapy Asia 2019 in Kobe, JapanKobe, JapanSELECTBIOenquiries@selectbiosciences.com
Add to Calendar ▼2019-11-12 14:30:002019-11-12 15:30:00Europe/LondonGeneration of CTLs from iPSCs Transduced with TCR Genes: Toward the Development of “Off-the-Shelf T Cells”Cell and Gene Therapy Asia 2019 in Kobe, JapanKobe, JapanSELECTBIOenquiries@selectbiosciences.com
