A paradigm shift in T cell adaptive cell therapy using Th1/Th17 cells transduced chimeric antigen receptor
Project/Area Number |
25670553
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Research Category |
Grant-in-Aid for Challenging Exploratory Research
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Allocation Type | Multi-year Fund |
Research Field |
General surgery
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Research Institution | Mie University |
Principal Investigator |
KATO Takuma 三重大学, 医学(系)研究科(研究院), 准教授 (60224515)
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Co-Investigator(Kenkyū-buntansha) |
WANG Linan 三重大学, 大学院医学系研究科, 特任助教(研究担当) (00589484)
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Project Period (FY) |
2013-04-01 – 2015-03-31
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Project Status |
Completed (Fiscal Year 2014)
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Budget Amount *help |
¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000)
Fiscal Year 2014: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2013: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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Keywords | キメラ抗原受容体 / T細胞輸注療法 / 癌胎児性抗原 |
Outline of Final Research Achievements |
CEA is cell surface antigens highly expressed on various cancer cell types but also expressed on healthy tissues, thus its feasibility as a target for CAR-modified T cell therapy will be required to augment efficacy, but also awaited before establishing its safety in terms of on-target-off-tumor effects. In the present study, we sought to determine whether CAR-CD4 T cells act in concert with CAR-CD8 T cells to exert anti-tumor activity in vivo using CEA-transgenic mouse expressing CEA as a self-antigen. The adoptive transfer of CEA specific CAR expression CD4 T cells did not enhance the efficacy of CEA-specific CAR-expressing CD8 T cells to exert anti-tumor activity. The adoptive transfer in conjunction with lymphodepleting preconditioning mediated significant tumor regression but caused weight loss in CEA-Tg mice. This weight loss was not associated with overt inflammation in CEA-expressing tissues, but malnutrition with elevated systemic levels of cytokines linked to anorexia.
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Report
(3 results)
Research Products
(16 results)
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[Journal Article] Interleukin-17 Induces an Atypical M2-Like Macrophage Subpopulation That Regulates Intestinal Inflammation.2014
Author(s)
Nishikawa K, Seo N, Torii M, Ma N, Muraoka D, Tawara I, Masuya M, Tanaka K, Takei Y, Shiku H, Katayama N, Kato T.
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Journal Title
PLOS ONE
Volume: 9
Issue: 9
Pages: e108494-e108494
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Overcoming regulatory T-cell suppression by a lyophilized preparation of Streptococcus pyogenes2013
Author(s)
Hirayama M, Nishikawa H, Nagata Y, Tsuji T, Kato T, Kageyama S, Ueda S, Sugiyama D, Hori S, Sakaguchi S, Ritter G, Old LJ, Gnjatic S, and Shiku H
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Journal Title
Eur J Immunol
Volume: 43 (4)
Issue: 4
Pages: 989-1000
DOI
Related Report
Peer Reviewed
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[Presentation] Efficacy and safety of T cells with CEA-specific chimeric antigen receptor for cancer immunotherapy2015
Author(s)
L. Wang, T. Kato, N. Seo, S. Okamoto, Y. Amaishi, J. Mineno, K. Takesako, H. Shiku
Organizer
Cell Symposia: Cancer, inflammation, and Immunity
Place of Presentation
Stiges, Sapin
Year and Date
2015-06-14 – 2015-06-16
Related Report
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[Presentation] Interleukin-17 induces an atypical M2-like macrophage subpopulation that regulates intestinal inflammation2015
Author(s)
Nishikawa K, Seo N, Torii M, Ma N, Muraoka D, Tawara I, Masuya M, Tanaka K, Takei Y, Shiku H, Katayama N, Kato T
Organizer
World Immune Regulation Meeting IX
Place of Presentation
Davos, Switzerland
Year and Date
2015-03-18 – 2015-03-21
Related Report
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