TS-2021, a third-generation oncolytic adenovirus that carried Ki67 promoter, TGF-β2 5'UTR, and IL-15 against experimental glioblastoma
© 2023 Wiley Periodicals LLC..
Oncolytic virotherapy is a promising therapeutic approach for glioblastoma (GBM) treatment, although the outcomes are partially satisfactory. Hence, more effective strategies are needed urgently to modify therapeutic viruses to enhance their efficiency and safety in killing tumor cells and improve the survival rate of GBM patients. This study generated a new-generation oncolytic adenovirus Ad5 KT-E1A-IL-15 (TS-2021) and evaluated its antitumor efficacy. Ex vivo analyses revealed Ki67 and TGF-β2 co-localized in GBM cells. In addition, TS-2021 selectively replicated in GBM cells, which was dependent on the expression of Ki67 and TGF-β2. The immunocompetent mice model of GBM demonstrated the in vivo efficacy of TS-2021 by inhibiting tumor growth and improving survival proficiently. Notably, TS-2021 effectively reduced MMP3 expression by inactivating the MKK4/JNK pathway, thereby reducing tumor invasiveness. Altogether, the findings of the present study highlight that TS-2021 can effectively target GBM cells expressing high levels of Ki67 and TGF-β2, exerting potent antitumor effects. Additionally, it can improve efficacy and suppress tumor invasiveness by inhibiting the MKK4/JNK/MMP3 pathway. Thus our study demonstrates the efficiency of the novel TS-2021 in the mouse model and provides a potential therapeutic option for patients with GBM.
| Medienart: |
E-Artikel |
|---|
| Erscheinungsjahr: |
2024 |
|---|---|
| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:96 |
|---|---|
| Enthalten in: |
Journal of medical virology - 96(2024), 1 vom: 09. Jan., Seite e29335 |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Wang, Jialin [VerfasserIn] |
|---|
| Links: |
|---|
| Anmerkungen: |
Date Completed 28.12.2023 Date Revised 14.02.2024 published: Print Citation Status MEDLINE |
|---|
| doi: |
10.1002/jmv.29335 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
NLM366401076 |
|---|
| LEADER | 01000caa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM366401076 | ||
| 003 | DE-627 | ||
| 005 | 20240214233031.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 231229s2024 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1002/jmv.29335 |2 doi | |
| 028 | 5 | 2 | |a pubmed24n1293.xml |
| 035 | |a (DE-627)NLM366401076 | ||
| 035 | |a (NLM)38149454 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Wang, Jialin |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a TS-2021, a third-generation oncolytic adenovirus that carried Ki67 promoter, TGF-β2 5'UTR, and IL-15 against experimental glioblastoma |
| 264 | 1 | |c 2024 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ƒaComputermedien |b c |2 rdamedia | ||
| 338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Date Completed 28.12.2023 | ||
| 500 | |a Date Revised 14.02.2024 | ||
| 500 | |a published: Print | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a © 2023 Wiley Periodicals LLC. | ||
| 520 | |a Oncolytic virotherapy is a promising therapeutic approach for glioblastoma (GBM) treatment, although the outcomes are partially satisfactory. Hence, more effective strategies are needed urgently to modify therapeutic viruses to enhance their efficiency and safety in killing tumor cells and improve the survival rate of GBM patients. This study generated a new-generation oncolytic adenovirus Ad5 KT-E1A-IL-15 (TS-2021) and evaluated its antitumor efficacy. Ex vivo analyses revealed Ki67 and TGF-β2 co-localized in GBM cells. In addition, TS-2021 selectively replicated in GBM cells, which was dependent on the expression of Ki67 and TGF-β2. The immunocompetent mice model of GBM demonstrated the in vivo efficacy of TS-2021 by inhibiting tumor growth and improving survival proficiently. Notably, TS-2021 effectively reduced MMP3 expression by inactivating the MKK4/JNK pathway, thereby reducing tumor invasiveness. Altogether, the findings of the present study highlight that TS-2021 can effectively target GBM cells expressing high levels of Ki67 and TGF-β2, exerting potent antitumor effects. Additionally, it can improve efficacy and suppress tumor invasiveness by inhibiting the MKK4/JNK/MMP3 pathway. Thus our study demonstrates the efficiency of the novel TS-2021 in the mouse model and provides a potential therapeutic option for patients with GBM | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a IL-15 | |
| 650 | 4 | |a JNK MAPK | |
| 650 | 4 | |a MMP3 | |
| 650 | 4 | |a glioma | |
| 650 | 4 | |a oncolytic adenovirus | |
| 650 | 7 | |a 5' Untranslated Regions |2 NLM | |
| 650 | 7 | |a Ki-67 Antigen |2 NLM | |
| 650 | 7 | |a Matrix Metalloproteinase 3 |2 NLM | |
| 650 | 7 | |a EC 3.4.24.17 |2 NLM | |
| 650 | 7 | |a Transforming Growth Factor beta2 |2 NLM | |
| 650 | 7 | |a Interleukin-15 |2 NLM | |
| 700 | 1 | |a Zhang, Junwen |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Qing |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Wenxin |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Qi |e verfasserin |4 aut | |
| 700 | 1 | |a Jin, Guishan |e verfasserin |4 aut | |
| 700 | 1 | |a Liu, Fusheng |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t Journal of medical virology |d 1990 |g 96(2024), 1 vom: 09. Jan., Seite e29335 |w (DE-627)NLM000285676 |x 1096-9071 |7 nnns |
| 773 | 1 | 8 | |g volume:96 |g year:2024 |g number:1 |g day:09 |g month:01 |g pages:e29335 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.1002/jmv.29335 |3 Volltext |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |d 96 |j 2024 |e 1 |b 09 |c 01 |h e29335 | ||