Organization
Graduate School of Medicine Designated professor
Title
Designated professor
NAOE Yoshinori
Degree 1
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博士（薬学） （ 1999.9 京都大学 ）
Papers 19
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STING activator 2′3′-cGAMP enhanced HSV-1-based oncolytic viral therapy
Sibal, PA; Matsumura, S; Ichinose, T; Bustos-Villalobos, I; Morimoto, D; Eissa, IR; Abdelmoneim, M; Aboalela, MAM; Mukoyama, N; Tanaka, M; Naoe, Y; Kasuya, H
MOLECULAR ONCOLOGY Vol. 18 ( 5 ) page： 1259 - 1277 2024.5
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The Impact of Metformin on Tumor-Infiltrated Immune Cells: Preclinical and Clinical Studies
Abdelmoneim, M; Aboalela, MA; Naoe, Y; Matsumura, S; Eissa, IR; Bustos-Villalobos, I; Sibal, PA; Takido, Y; Kodera, Y; Kasuya, H
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES Vol. 24 ( 17 ) 2023.9
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Aboalela, MA; Abdelmoneim, MA; Naoe, Y; Matsumura, S; Kasuya, H
CANCER SCIENCE Vol. 114 page： 994 - 994 2023.2
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Novel new cell therapy of chimeric antigen receptors into dendritic cells
Naoe, Y; Abdelmoneim, MA; Aboalela, M; Eissa, IR; Matsumura, S; Kasuya, H
CANCER SCIENCE Vol. 114 page： 997 - 997 2023.2
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Novel armed oncolytic HSV exhibits strong antitumor effects that lead to complete tumor regression
Abdelmoneim, MA; Naoe, Y; Eissa, IR; Aboalela, MA; Matsumura, S; Tanaka, M; Kasuya, H
CANCER SCIENCE Vol. 114 page： 1855 - 1855 2023.2
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Aboalela, MA; Abdelmoneim, MA; Naoe, Y; Matsumura, S; Kasuya, H
CANCER SCIENCE Vol. 114 page： 1419 - 1419 2023.2
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Abdelmoneim, M; Eissa, IR; Aboalela, MA; Naoe, Y; Matsumura, S; Sibal, PA; Bustos-Villalobos, I; Tanaka, M; Kodera, Y; Kasuya, H
SCIENTIFIC REPORTS Vol. 12 ( 1 ) 2022.12
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Mohamed, AA; Eissa, IR; Mukoyama, N; Abdelmoneim, M; Naoe, Y; Matsumura, S; Bustosvillalobos, I; Ichinose, T; Miyajima, N; Morimoto, D; Tanaka, M; Fujimoto, Y; Sone, M; Kodera, Y; Kasuya, H
CANCER SCIENCE Vol. 113 page： 526 - 526 2022.2
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Miyajima, N; Eissa, IR; Abdelmoneim, M; Naoe, Y; Ichinose, T; Matsumura, S; Bustos-Villalobos, I; Mukoyama, N; Morimoto, D; Shibata, M; Takeuchi, D; Tsunoda, N; Kikumori, T; Tanaka, M; Kodera, Y; Kasuya, H
NAGOYA JOURNAL OF MEDICAL SCIENCE Vol. 83 ( 4 ) page： 683 - 696 2021.11
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Eissa, IR; Mukoyama, N; Abdelmoneim, M; Naoe, Y; Matsumura, S; Bustos-Villalobos, I; Ichinose, T; Miyajima, N; Morimoto, D; Tanaka, M; Fujimoto, Y; Sone, M; Kodera, Y; Kasuya, H
INTERNATIONAL JOURNAL OF CANCER Vol. 149 ( 1 ) page： 214 - 227 2021.7
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Morimoto, D; Matsumura, S; Bustos-Villalobos, I; Sibal, PA; Ichinose, T; Naoe, Y; Eissa, IR; Abdelmoneim, M; Mukoyama, N; Miyajima, N; Tanaka, M; Kodera, Y; Kasuya, H
CELLS Vol. 10 ( 6 ) 2021.6
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S-1 Facilitates C-REV Induced Anti-Tumor Efficacy in Triple Negative Breast Cancer Model
Kasuya, H; Naoe, Y; Matsumura, S; Bustos, I; Eissa, I; Mohamed, A; Tanaka, M
MOLECULAR THERAPY Vol. 28 ( 4 ) page： 163 - 163 2020.4
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Wu, ZW; Ichinose, T; Naoe, Y; Matsumura, S; Villalobos, IB; Eissa, IR; Yamada, S; Miyajima, N; Morimoto, D; Mukoyama, N; Nishikawa, Y; Koide, Y; Kodera, Y; Tanaka, M; Kasuya, H
MOLECULAR THERAPY-ONCOLYTICS Vol. 13 page： 107 - 115 2019.6
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Eissa, IR; Bustos-Villalobos, I; Ichinose, T; Matsumura, S; Naoe, Y; Miyajima, N; Morimoto, D; Mukoyama, N; Wu, ZW; Tanaka, M; Hasegawa, H; Sumigama, S; Aleksic, B; Kodera, Y; Kasuya, H
CANCERS Vol. 10 ( 10 ) 2018.10
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WAIF1 Is a Cell-Surface CTHRC1 Binding Protein Coupling Bone Resorption and Formation.
Matsuoka K, Kohara Y, Naoe Y, Watanabe A, Ito M, Ikeda K, Takeshita S
Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research Vol. 33 ( 8 ) page： 1500 - 1512 2018.8
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Hirooka, Y; Kasuya, H; Ishikawa, T; Kawashima, H; Ohno, E; Villalobos, IB; Naoe, Y; Ichinose, T; Koyama, N; Tanaka, M; Kodera, Y; Goto, H
BMC CANCER Vol. 18 ( 1 ) page： 596 2018.5
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Priming of lineage-specifying genes by Bcl11b is required for lineage choice in post-selection thymocytes.
Kojo S, Tanaka H, Endo TA, Muroi S, Liu Y, Seo W, Tenno M, Kakugawa K, Naoe Y, Nair K, Moro K, Katsuragi Y, Kanai A, Inaba T, Egawa T, Venkatesh B, Minoda A, Kominami R, Taniuchi I
Nature communications Vol. 8 ( 1 ) page： 702 2017.9
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Genomic Signature of the Natural Oncolytic Herpes Simplex Virus HF10 and Its Therapeutic Role in Preclinical and Clinical Trials.
Eissa IR, Naoe Y, Bustos-Villalobos I, Ichinose T, Tanaka M, Zhiwen W, Mukoyama N, Morimoto T, Miyajima N, Hitoki H, Sumigama S, Aleksic B, Kodera Y, Kasuya H
Frontiers in oncology Vol. 7 page： 149 2017
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Curative effect of HF10 on liver and peritoneal metastasis mediated by host antitumor immunity
Hotta Yoshihiro, Kasuya Hideki, Bustos Itzel, Naoe Yoshinori, Ichinose Toru, Tanaka Maki, Kodera Yasuhiro
ONCOLYTIC VIROTHERAPY Vol. 6 page： 31 - 38 2017
KAKENHI (Grants-in-Aid for Scientific Research) 4
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固形癌に対するCAR-T、ウイルス療法の併用による新規免疫療法の開発
Grant number：21H02999 2021.4 - 2024.3
科学研究費助成事業 基盤研究(B)
粕谷 英樹, 直江 吉則, 松村 繁
Authorship：Coinvestigator(s)
本研究は、腫瘍溶解性ウイルスとCAR-T細胞との併用でより強力な癌免疫療法を確立することを目的とし、T細胞の集族を向上させるケモカインRANTESとT細胞誘導標識抗原とを同時に発現する次世代型腫瘍溶解性ウイルスを開発することによって、CAR-T細胞を意図的に腫瘍に集簇させ、これに派生する以下の問いに解答を得ることで医療に貢献すると共に、幅広く研究者に有益な学術的情報を提供する。
本研究は細胞療法や免疫チェックポイント阻害薬が十分な効果を発揮できないアンメットメディカルニーズ難治固形癌の新たな治療法を開発することを目的に、癌抗原とケモカインを同時に搭載した次世代型腫瘍溶解性ウイルスと標識癌抗原を認識するCAR-Tを新たに創造することである。昨年度、野生型HSV1のg34.5遺伝子座にCMVプロモーターにより発現するヒトMesothelin(MSLN)を導入した腫瘍溶解性ウイルス作成した(HSV1-MSLN)。このウイルスは感染した腫瘍でMSLNが発現することを確認した。また、ヒトMSLNに対する一本鎖抗体にCD28膜貫通領域、さらに、CD3細胞内ドメインをタンデムに結合させたレトロウイルスベクターを作成、マウスT細胞に感染させ、ヒトMSLNに対するCAR-T細胞を作製した。このCAR-T細胞はMSLN発現細胞と共培養することにより活性化することを確認した。本年度は、HSV1-MSLNとCAR-T細胞の併用効果をin vivoにおいて評価した。HSV1-MSLNは担癌マウスに投与しても体重減少を起こさなかったことから、安全性は高かった。マウス皮下にマウス膵臓癌細胞Pan02を移植し、腫瘍の大きさが100mm3の大きさに達した時点でHSV1-MSLNを腫瘍内に投与した。その後CAR-T細胞を腫瘍内に投与し、腫瘍の増殖を経時的に測定した。その結果、HSV1-MSLN単独ならびにHSV1-MSLN/CAR-T細胞併用は腫瘍の増殖を著しく抑制した。しかし、HSV1-MSLN/CAR-T細胞併用はHSV1-MSLN単独よりも強い抗腫瘍効果を発揮したが、HSV1-MSLN単独でも強い抗腫瘍効果を発揮したため、優位な併用効果を確認することが出来なかった。
ヒトMSLN発現腫瘍溶解性ウイルスとヒトMSLN認識CAR-T細胞を併用することにより、in vivoにおいて強い抗腫瘍効果を確認することができた。
本年度は抗原発現腫瘍溶解性ウイルスとCAR-T細胞の併用効果をin vivoで確認できた。今後、併用治療がウイルス単独治療より優位な効果を発揮するかどうか、ウイルスの投与量、投与スケジュールを検討し併用効果を確認する予定である。また、より強い併用効果を発揮するためにウイルスにCAR-T細胞を腫瘍内に誘導するためのケモカインを搭載する。 -
Role of intestinal flora on the antitumor immunity of oncolytic viruses
Grant number：19H03434 2019.4 - 2022.3
Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (B)
Naoe Yoshinori
Authorship：Principal investigator
Grant amount：\17550000 （ Direct Cost: \13500000 、 Indirect Cost：\4050000 ）
Changes in the intestinal flora were observed by administration of C-REV to antibiotic-treated mice in the intraperitoneal transplant model and the subcutaneous transplant model. The antitumor effect of C-REV changes depending on the combination of the four antibiotics Ampicillin (A), Metronidazole (M), Neomycin (N), or Vancomycin (V), and the order of the effect is (large effect) AMNV = AMV > MNV > ANV = AMN (small effect). The difference in the bacterial flora of the mice by the antibiotic cocktail treatment was found, and a large change was observed in the bacterial flora with and without the antibiotic cocktail treatment.
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Oncolytic virus targeting tumor associated mesenchymal stem cells
Grant number：18H02691 2018.4 - 2022.3
Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (B)
Matsumura Shigeru
Authorship：Coinvestigator(s)
One of the mechanisms for immune suppression in pancreatic tumors is the recruitment of mesenchymal stem cells (MSC), which turn into tumor-associated fibroblasts. C-REV, our oncolytic virus, has been shown to dramatically change the tumor microenvironment. Here, we examined whether C-REV has the ability to kill MSC in the tumor tissue. A naturally mutated attenuated HSV1, C-REV cannot replicate inside the healthy normal cells. However, we found that C-REV can infect and replicate in the MSC. Furthermore, C-REV treatment on the MSC-injected pancreatic tumors showed decreased numbers of MSC in the mouse model.
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TCR sequencing of tumor infiltrating T cells using iPS cell technology
Grant number：17K19696 2017.6 - 2019.3
Grant-in-Aid for Challenging Research (Exploratory)
Naoe Yoshinori
Authorship：Principal investigator
Grant amount：\6500000 （ Direct Cost: \5000000 、 Indirect Cost：\1500000 ）
By collecting tumor-specific cytotoxic T cells infiltrating the mouse tumor and introducing Yamanaka factor, it was possible to obtain a cell population that proliferates without anti-CD3 antibody stimulation. These cells were judged as iPS cells because they proliferated without TCR stimulation. In addition, we confirmed a gene rearrangement of the TCRb in all the proliferating cells examined. From the above, it was suggested that cells proliferating without anti-CD3 stimulation are derived from T cells. In addition, we tried to establish iPS cells using human peripheral cytotoxic T cells, but the establishment efficiency was low. In the future, we will investigate culture conditions and try to improve the establishment efficiency.