Enhanced potency of immune checkpoint inhibitors against poorly immunological solid tumors by immune stimulatory oncolytic adenoviruses-mediated remodeling of the tumor microenvironment
Abstract Immune checkpoint inhibitor (ICI) have shown promising results against a variety of solid tumors across clinical trials. However, ICI monotherapy is often ineffective in patients with non-immunogenic tumors that exhibit high level of immunosuppression and low level of tumor infiltrating lym...
Saved in:
| Main Authors: | , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
BMC
2025-05-01
|
| Series: | Molecular Medicine |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s10020-025-01223-4 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1849729120435437568 |
|---|---|
| author | Hyo Min Ahn Bo-Kyeong Jung JinWoo Hong Dayoung Hong A-Rum Yoon Chae-Ok Yun |
| author_facet | Hyo Min Ahn Bo-Kyeong Jung JinWoo Hong Dayoung Hong A-Rum Yoon Chae-Ok Yun |
| author_sort | Hyo Min Ahn |
| collection | DOAJ |
| description | Abstract Immune checkpoint inhibitor (ICI) have shown promising results against a variety of solid tumors across clinical trials. However, ICI monotherapy is often ineffective in patients with non-immunogenic tumors that exhibit high level of immunosuppression and low level of tumor infiltrating lymphocytes. To address these limitations, we have investigated a combination of ICIs [anti-PD-1 antibody (αPD-1), anti-PD-L1 antibody (αPD-L1), or anti-CTLA-4 antibody (αCTLA-4)] with several different immune stimulatory oncolytic adenoviruses (Ads) expressing different combinations of antitumor cytokines or immune modulatory factors [e.g., (1) interleukin (IL)-12 and granulocyte-macrophage colony-stimulating factor (GM-CSF; RdB/IL12/GMCSF), (2) IL-12 and short hairpin ribonucleic acid (shRNA) targeting vascular endothelial growth factor (RdB/IL12/shVEGF), (3) IL-12 and decorin (RdB/IL12/DCN), (4) GM-CSF, and thymidine kinase (RdB/IL12/GMCSF-TK), or (5) IL-12, GM-CSF, and relaxin (RdB/IL12/GMCSF-RLX)] to overcome tumor-induced immunosuppression. Through comparative evaluation of combination therapy regimens, our findings have identified αPD-1 as the optimal ICI candidate to synergize with different oncolytic Ads to induce potent antitumor immune response against poorly immunological solid tumors. |
| format | Article |
| id | doaj-art-aadbd973dd1241b9846f2dca0513a9b5 |
| institution | DOAJ |
| issn | 1528-3658 |
| language | English |
| publishDate | 2025-05-01 |
| publisher | BMC |
| record_format | Article |
| series | Molecular Medicine |
| spelling | doaj-art-aadbd973dd1241b9846f2dca0513a9b52025-08-20T03:09:19ZengBMCMolecular Medicine1528-36582025-05-0131112110.1186/s10020-025-01223-4Enhanced potency of immune checkpoint inhibitors against poorly immunological solid tumors by immune stimulatory oncolytic adenoviruses-mediated remodeling of the tumor microenvironmentHyo Min Ahn0Bo-Kyeong Jung1JinWoo Hong2Dayoung Hong3A-Rum Yoon4Chae-Ok Yun5GeneMedicine Co., LtdGeneMedicine Co., LtdGeneMedicine Co., LtdDepartment of Bioengineering, College of Engineering, Hanyang UniversityDepartment of Bioengineering, College of Engineering, Hanyang UniversityDepartment of Bioengineering, College of Engineering, Hanyang UniversityAbstract Immune checkpoint inhibitor (ICI) have shown promising results against a variety of solid tumors across clinical trials. However, ICI monotherapy is often ineffective in patients with non-immunogenic tumors that exhibit high level of immunosuppression and low level of tumor infiltrating lymphocytes. To address these limitations, we have investigated a combination of ICIs [anti-PD-1 antibody (αPD-1), anti-PD-L1 antibody (αPD-L1), or anti-CTLA-4 antibody (αCTLA-4)] with several different immune stimulatory oncolytic adenoviruses (Ads) expressing different combinations of antitumor cytokines or immune modulatory factors [e.g., (1) interleukin (IL)-12 and granulocyte-macrophage colony-stimulating factor (GM-CSF; RdB/IL12/GMCSF), (2) IL-12 and short hairpin ribonucleic acid (shRNA) targeting vascular endothelial growth factor (RdB/IL12/shVEGF), (3) IL-12 and decorin (RdB/IL12/DCN), (4) GM-CSF, and thymidine kinase (RdB/IL12/GMCSF-TK), or (5) IL-12, GM-CSF, and relaxin (RdB/IL12/GMCSF-RLX)] to overcome tumor-induced immunosuppression. Through comparative evaluation of combination therapy regimens, our findings have identified αPD-1 as the optimal ICI candidate to synergize with different oncolytic Ads to induce potent antitumor immune response against poorly immunological solid tumors.https://doi.org/10.1186/s10020-025-01223-4Checkpoint inhibitorsOncolytic adenovirusProgrammed cell death protein 1Programmed death-ligand 1Cytotoxic T lymphocyte-associated protein 4Combination therapy |
| spellingShingle | Hyo Min Ahn Bo-Kyeong Jung JinWoo Hong Dayoung Hong A-Rum Yoon Chae-Ok Yun Enhanced potency of immune checkpoint inhibitors against poorly immunological solid tumors by immune stimulatory oncolytic adenoviruses-mediated remodeling of the tumor microenvironment Molecular Medicine Checkpoint inhibitors Oncolytic adenovirus Programmed cell death protein 1 Programmed death-ligand 1 Cytotoxic T lymphocyte-associated protein 4 Combination therapy |
| title | Enhanced potency of immune checkpoint inhibitors against poorly immunological solid tumors by immune stimulatory oncolytic adenoviruses-mediated remodeling of the tumor microenvironment |
| title_full | Enhanced potency of immune checkpoint inhibitors against poorly immunological solid tumors by immune stimulatory oncolytic adenoviruses-mediated remodeling of the tumor microenvironment |
| title_fullStr | Enhanced potency of immune checkpoint inhibitors against poorly immunological solid tumors by immune stimulatory oncolytic adenoviruses-mediated remodeling of the tumor microenvironment |
| title_full_unstemmed | Enhanced potency of immune checkpoint inhibitors against poorly immunological solid tumors by immune stimulatory oncolytic adenoviruses-mediated remodeling of the tumor microenvironment |
| title_short | Enhanced potency of immune checkpoint inhibitors against poorly immunological solid tumors by immune stimulatory oncolytic adenoviruses-mediated remodeling of the tumor microenvironment |
| title_sort | enhanced potency of immune checkpoint inhibitors against poorly immunological solid tumors by immune stimulatory oncolytic adenoviruses mediated remodeling of the tumor microenvironment |
| topic | Checkpoint inhibitors Oncolytic adenovirus Programmed cell death protein 1 Programmed death-ligand 1 Cytotoxic T lymphocyte-associated protein 4 Combination therapy |
| url | https://doi.org/10.1186/s10020-025-01223-4 |
| work_keys_str_mv | AT hyominahn enhancedpotencyofimmunecheckpointinhibitorsagainstpoorlyimmunologicalsolidtumorsbyimmunestimulatoryoncolyticadenovirusesmediatedremodelingofthetumormicroenvironment AT bokyeongjung enhancedpotencyofimmunecheckpointinhibitorsagainstpoorlyimmunologicalsolidtumorsbyimmunestimulatoryoncolyticadenovirusesmediatedremodelingofthetumormicroenvironment AT jinwoohong enhancedpotencyofimmunecheckpointinhibitorsagainstpoorlyimmunologicalsolidtumorsbyimmunestimulatoryoncolyticadenovirusesmediatedremodelingofthetumormicroenvironment AT dayounghong enhancedpotencyofimmunecheckpointinhibitorsagainstpoorlyimmunologicalsolidtumorsbyimmunestimulatoryoncolyticadenovirusesmediatedremodelingofthetumormicroenvironment AT arumyoon enhancedpotencyofimmunecheckpointinhibitorsagainstpoorlyimmunologicalsolidtumorsbyimmunestimulatoryoncolyticadenovirusesmediatedremodelingofthetumormicroenvironment AT chaeokyun enhancedpotencyofimmunecheckpointinhibitorsagainstpoorlyimmunologicalsolidtumorsbyimmunestimulatoryoncolyticadenovirusesmediatedremodelingofthetumormicroenvironment |