Optimization of tumor-infiltrating of cytotoxic T cells using capacity of the anti-mesenchymal tumor stromal cells of CD8+ T cell exosomes
| Project/Area Number |
18K19474
|
|---|
| Research Category |
Grant-in-Aid for Challenging Research (Exploratory)
|
| Allocation Type | Multi-year Fund |
|---|
| Review Section |
Medium-sized Section 50:Oncology and related fields
|
|---|
| Research Institution | Mie University |
|---|
Principal Investigator |
Seo Naohiro 三重大学, 医学系研究科, 産学官連携講座講師 (50283354)
|
|---|
| Project Period (FY) |
2018-06-29 – 2021-03-31
|
| Project Status |
Completed (Fiscal Year 2020)
|
| Budget Amount *help |
¥6,240,000 (Direct Cost: ¥4,800,000、Indirect Cost: ¥1,440,000)
Fiscal Year 2019: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
Fiscal Year 2018: ¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000)
|
|---|
| Keywords | 細胞外小胞 / エクソソーム / がん / がん間質 / がん関連線維芽細胞 / 間葉系幹細胞 / CAR-T細胞 / がん細胞 / がん間質細胞 / がん実質 / 細胞傷害性T細胞 / 免疫細胞療法 / がん免疫 / CD8+ T細胞 |
|---|
| Outline of Final Research Achievements |
Administration of normal CD8+ T cell exosomes to tumor lesions showed no dramatic improvement in T cell infiltration of tumor. We decided to conduct an experiment using exosomes obtained from the culture supernatant of CAR-T cells that had been given specificity to the tumor cells. It was revealed that CAR-T cell exosomes have a dual cytotoxic function of CAR-specific tumor cells as well as stromal cells such as CAF and MSC. CAR-T cell exosomes have a possibility to be an effective adjuvant for modulating tumor microenvironment in T cell therapy, and we are currently conducting research.
|
| Academic Significance and Societal Importance of the Research Achievements |
がん組織は、がん細胞からなるがん実質とがん関連線維芽細胞(CAF)や間葉系幹細胞(MSC)などからなるがん間質からなり、それらが、どのように協調しがん組織を形成し、抗腫瘍免疫応答に対する回避機構を獲得しているのかについては、未だ変わらないことが多い。本研究は、非特異的なCD8+ T細胞エクソソームからがん細胞に特異的なCAR-T細胞の放出するエクソソームへと使用するエクソソームを変更したが、エクソソームのがん間質細胞に取り込まれやすい性質は、がんの微小環境の理解を深めることはもちろん、がん治療の補助剤としての利用価値もあり、学術的にも社会的にも重要だと考えている。
|
Report
(4 results)
Research Products
(13 results)
-
-
-
-
-
[Journal Article] Antitumor activity of CAR-T cells targeting the intracellular oncoprotein WT1 can be enhanced by vaccination.2018
Author(s)
Akahori Y, Wang L, Yoneyama M, Seo N, Okumura S, Miyahara Y, Amaishi Y, Okamoto S, Mineno J, Ikeda H, Maki T, Fujiwara H, Akatsuka Y, Kato T, Shiku H.
-
Journal Title
Blood. 2018 Sep 13;132(11):
Volume: 132
Issue: 11
Pages: 1134-1145
DOI
Related Report
Peer Reviewed / Open Access
-
-
-
-
-
-
-
-
