The efficacy and safety of iPSC-derived CART therapy for small cell lung cancer
| Project/Area Number |
19K07781
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Multi-year Fund |
|---|
| Section | 一般 |
|---|
| Review Section |
Basic Section 50020:Tumor diagnostics and therapeutics-related
|
|---|
| Research Institution | Juntendo University |
|---|
Principal Investigator |
Ando Miki 順天堂大学, 医学部, 教授 (10424251)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
安藤 純 順天堂大学, 医学部, 教授 (60348943)
|
|---|
| Project Period (FY) |
2019-04-01 – 2022-03-31
|
| Project Status |
Completed (Fiscal Year 2021)
|
| Budget Amount *help |
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2021: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2020: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
|
|---|
| Keywords | キメラ抗原受容体T細胞 / 小細胞肺がん / GD2-CAR / T-iPSC / 若返りCTL / T-iPS |
|---|
| Outline of Research at the Start |
本研究では小細胞肺がんの多くが細胞表面に糖鎖抗原であるGD2を発現することに着目し、先行技術の応用によりiPS細胞にGD2-CARを遺伝子導入後、若返りGD2-CARTを分化誘導し、小細胞肺がんに強力な治療となりうるか検証する。また、副作用発現時もしくはCARTが不要になった場合に体内から消失できるよう、自殺遺伝子細胞死誘導システムを備え、安全性と有効性の両方を担保できる画期的な治療の基礎開発を行う。
|
| Outline of Final Research Achievements |
We have reported that iPSC-derived dual-antigen receptor rejuvenated T cells (rejTs) can target CD19 antigen via chimeric antigen receptor (CAR) and Epstein-Barr LMP2 antigen via native TCR, resulting in robust anti-tumor effect against EBV-associated lymphoma (Harada et al., Molecular Therapy, 2021). Applying this strategy to GD2 positive refractory tumors, we generated iPSC-derived GD2-CAR-rejTs and examined the efficacy and safety against GD2-positive small cell lung cancer (SCLC). Peripheral blood-derived GD2-CARTs did not show cytotoxicity against SCLC cell lines, whereas GD2-CAR-rejTs showed much stronger cytotoxicity against SCLC cell lines than that of peripheral blood-derived GD2-CARTs in vitro. Furthermore, GD2-CAR-rejTs successfully suppressed tumor growth in vivo compared to untreated mice. This approach would be a promising therapy for refractory SCLC.
|
| Academic Significance and Societal Importance of the Research Achievements |
小細胞肺がんは肺がんの中で最も進行が速く、多くの患者は再発し治療抵抗性を示す。5年生存率は７％以下と極めて予後不良にも関わらず、新規治療開発から長らく取り残されてきた。本研究では小細胞肺がんの多くが細胞表面にGD2を発現することに着目し、iPSCにGD2-CARを遺伝子導入後GD2-CARTを分化誘導し、小細胞肺がんに強力な治療となりうるか検証した。末梢血GD2-CARTは小細胞肺がんに細胞傷害活性を示さなかったが、iPSC由来GD2-CARTは強い細胞傷害活性を示した。小細胞肺がんに対する新規治療となりうる有望な結果であり、その抗腫瘍効果の差について解析することも学問的に重要と考える。
|
Report
(4 results)
Research Products
(29 results)
-
-
-
-
-
[Journal Article] iPSC-Derived Neoantigen-Specific CTL Therapy for Ewing Sarcoma2021
Author(s)
Ishii Midori、Ando Jun、Yamazaki Satoshi、Toyota Tokuko、Ohara Kazuo、Furukawa Yoshiki、Suehara Yoshiyuki、Nakanishi Mahito、Nakashima Kazutaka、Ohshima Koichi、Nakauchi Hiromitsu、Ando Miki
-
Journal Title
Cancer Immunology Research
Volume: 9
Issue: 10
Pages: 1175-1186
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
-
[Journal Article] SCLC-J1, a novel small cell lung cancer cell line2021
Author(s)
Ohara Kazuo、Kinoshita Shintaro、Ando Jun、Azusawa Yoko、Ishii Midori、Harada Sakiko、Mitsuishi Yoichiro、Asao Tetsuhiko、Tajima Ken、Yamamoto Taketsugu、Takahashi Fumiyuki、Komatsu Norio、Takahashi Kazuhisa、Ando Miki
-
Journal Title
Biochemistry and Biophysics Reports
Volume: 27
Pages: 101089-101089
DOI
Related Report
Peer Reviewed / Open Access
-
[Journal Article] Long-term eradication of extranodal natural killer/T-cell lymphoma, nasal type, by induced pluripotent stem cell-derived Epstein-Barr virus-specific rejuvenated T cells in vivo2020
Author(s)
Ando M, Ando J, Yamazaki S, Ishii M, Sakiyama Y, Harada S, Honda T, Yamaguchi T, Nojima M, Ohshima K, Nakauchi H, Komatsu N
-
Journal Title
Haematologica
Volume: 105
Issue: 3
Pages: 796-807
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
-
-
-
[Journal Article] Sustainable tumor suppressive effect of iPSC-derived rejuvenated T cells targeting cervical cancers.2020
Author(s)
Tadahiro Honda, Miki Ando, Jun Ando, Midori Ishii, Yumi Sakiyama, Kazuo Ohara, Tokuko Toyota, Manami Ohtaka, Ayako Masuda, Yasuhisa Terao, Mahito Nakanishi, Hiromitsu Nakauchi, and Norio Komatsu
-
Journal Title
Molecular Therapy
Volume: 28
Issue: 11
Pages: 2394-2405
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
