News & Events
News & Events
December 13, 2022
Genetic modifications boosting CAR signaling improve the therapeutic efficacy of iPSC-derived CAR-T cells against solid tumors
In order to use T cells expressing chimeric antigen receptor (CAR) effectively in immunotherapy against solid tumors, it is critical for the intravenously administered CAR-T cells to accumulate and proliferate at the tumor site, where they will work continuously to target and eliminate the deleterious cancer cells.
The research group led by Professor Kaneko and Dr. Tatsuki Ueda, a former CiRA researcher now at the University of Chicago, began by examining whether different CAR constructs affected the differentiation of iPS cell-derived hematopoietic progenitor cells into T cells and ultimately selected one that did not have any negative impact on differentiation efficiency.
Next, the team successfully showed in a solid tumor mouse model that two additional genetic manipulations of these iCAR-T cells--designed to augment T cell activation--enhanced their proliferation at the tumor site and extended their survival longer than ever shown before. Strikingly, the modified iCAR-T cells suppressed tumor growth and prolonged the recipient animals' survival even when only 1/20th of the original dose tested for unmodified iCAR-T cells was administered.
These modifications designed by Kaneko's team are expected to make the long sought-after practical use of iPSC-derived CAR-T cells for solid tumor treatment one step closer to reality.
The results of this study were published online in Nature Biomedical Engineering on December 12, 2022.
- Journal: Nature Biomedical Engineering
- Title: Optimization of the proliferation and persistency of CAR T cells derived from human induced pluripotent stem cells
Tatsuki Ueda1,2, Sara Shiina1,3, Shoichi Iriguchi1,3, Seitaro Terakura4, Yohei Kawai1, Ryotaro Kabai5, Satoko Sakamoto5, Akira Watanabe5, Kohei Ohara1, Bo Wang1,3,
Huaigeng Xu1, Atsutaka Minagawa1, Akitsu Hotta1, Knut Woltjen1, Yasushi Uemura6, Yuzo Kodama7, Hiroshi Seno2, Tetsuya Nakatsura6, Koji Tamada8, Shin Kaneko1,3,*
*: Corresponding author
- Author Affiliations:
- Center for iPS Cell Research and Application (CiRA), Kyoto University
- Department of Gastroenterology and Hepatology, Kyoto University Graduate School of Medicine
- Takeda-CiRA Joint Program (T-CiRA)
- Nagoya University Graduate School of Medicine
- Medical Innovation Center, Kyoto University Graduate School of Medicine
- Exploratory Oncology Research and Clinical Trial Center, National Cancer Center
- Kobe University Graduate School of Medicine
- Yamaguchi University Graduate School of Medicine