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The goal of The Kaneko laboratory is to regenerate human immune system utilizing the iPSC technology.

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Department of Cell Growth and Differentiation,
Center for iPS Cell Research and Application,
Kyoto University
SHiN KANEKO Laboratory

53 Kawahara-cho, Shogoin Yoshida,
Sakyo-ku, Kyoto 606-8507, Japan

Tel +81-75-366-7157
Fax +81-75-366-7158
kaneko-g[at]cira.kyoto-u.ac.jp
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Research

The goal of The Kaneko laboratory is to regenerate human immune system utilizing the iPSC technology. The specific aims of the research are described below.

1. Regeneration of antigen-specific cytotoxic T lymphocytes for clinical applications.

When I was working as a staff scientist at Division of Stem Cell Therapy, Institute of Medical Sciences, the University of Tokyo (Prof. Hiromitsu Nakauchi), I have succeeded to generate a large amount of a cytotoxic CD8+ T lymphocyte clone specific to a HIV antigen by a novel T lymphocyte redifferentiation method of a iPSC established from the T lymphocyte clone isolated from a HIV-positive patient. Through the research, we found an elongation of telomere length of the T lymphocyte clone compared to its original T lymphocytes. It indicates rejuvenation of the original T lymphocytes and utility of the clone for adoptive immunotherapy (Nishimura T et al., Cell Stem Cell.12: 114-226. 2013). In order to translate this achievement to clinical applications, we are doing extensive research on further functional improvement of the cytotoxic T lymphocyte clone and establishment of other cytotoxic T lymphocyte clones specific to tumor antigens and viral antigens.

2. Regeneration and transdifferentiation of antigen specific CD4+ T lymphocyte subsets.

As opposed to cytotoxic CD8+ lymphocytes, which present with singular function, CD4+ T lymphocytes present with functional plasticity, including Th1, Th2, Th17, Treg, Tfh, and Th9 and orchestrate diverse immune responses. We are trying to develop a method to redifferentiate iPSCs into functional CD4+ T lymphocytes to establish CD4+ T lymphocyte clones capable of promoting or suppressing immune responses in an antigen-specific manner. In particular, we are focusing on intervening autoimmune diseases and post-transplant diseases by inducing transdifferentiation from a CD4 T lymphocyte subset to another in situ using the established clones while sustaining its antigen specificity.

3. Regeneration of T lymphocyte with invariant T cell receptor chains.

A subset of T lymphocytes recognizes lipids through invariant T cell receptors and it involves in modulation of a variety of immune responses. We have established iPSC clones from human V-alpha24+ invariant T lymphocytes and redifferentiated it into T lymphocytes. Currently, we are analyzing the immunological functions of the established clones.

4. Elucidation of the mechanism underlying chronic virus infections using macrophages and dendritic cells derived from iPSCs toward therapeutic interventions.

Although macrophages and dendritic cells serve as the first line of defense against invading pathogens, they have known to be exploited as a virus reservoir during chronic virus infections, such as HIV. Using macrophages and dendritic cells derived from iPSCs transduced with an infection-resistance gene, we are trying to elucidate mechanisms that underlie chronic infections and develop a novel therapeutic intervention.

5. Establishment of patient-specific iPSCs and Elucidation of pathological differentiation processes.

iPSC technology allow us to develop in vitro models for rare diseases. We have established iPSCs from patients with hematological disorders, in particular lymphocyte differentiation abnormality, and are making an attempt to recapitulate the pathological features parallel to the patient with main focuses on elucidation of pathogenesis toward development of new therapies.

6. Automation of iPSC culture and immune cell induction processes

Utilizing immune cells derived from iPSCs to drug discovery and cell-based therapies requires the facility that ensures the stable supply and consistent quality of these cells. To achieve this, we are working through the development of a closed culture system and its automation.