CARG-2020 targets IL-12, IL-17, and PD-L1 pathways to effectively treat melanoma and breast cancer
Abstract Cancer immunotherapy has recently achieved a breakthrough status, however, it is not effective in all cancer types. Genetically engineered oncolytic viruses (OVs) with immunomodulators are promising new therapeutic modalities for cancer. CARG-2020 is an engineered trivalent oncolytic viral...
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Nature Portfolio
2025-08-01
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| Online Access: | https://doi.org/10.1038/s41598-025-14750-1 |
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| author | Elham Ahmadi Conner Chiari Bhaskara Reddy Madina Timur Olegovich Yarovinsky Marie Marthe Krady Ju Chen Bijan Almassian Valerian Nakaar Kepeng Wang |
| author_facet | Elham Ahmadi Conner Chiari Bhaskara Reddy Madina Timur Olegovich Yarovinsky Marie Marthe Krady Ju Chen Bijan Almassian Valerian Nakaar Kepeng Wang |
| author_sort | Elham Ahmadi |
| collection | DOAJ |
| description | Abstract Cancer immunotherapy has recently achieved a breakthrough status, however, it is not effective in all cancer types. Genetically engineered oncolytic viruses (OVs) with immunomodulators are promising new therapeutic modalities for cancer. CARG-2020 is an engineered trivalent oncolytic viral construct that specifically expresses three immune modulators that inhibit IL-17RA signaling and regulate PD-L1 expression by shRNAs, along with the cytokine IL-12 which activates multiple tumoricidal pathways. Previous work showed that intratumoral (i.t.) injection of CARG-2020 exhibits robust efficacy against established colorectal cancer (CRC). In this study, we report that systemic delivery of CARG-2020 via the intravenous (i.v.) route can successfully control CRC growth. To further expand the scope of CARG-2020 as a pan-cancer candidate, we also show that CARG-2020 works in two additional mouse models of melanoma and triple-negative breast cancer. Administration of CARG-2020 resulted in increased accumulation of CD8+ T lymphocytes in the tumors, and depletion of these T cells results in poor tumor regression mediated by CARG-2020. Overall, our study shows a broad-spectrum efficacy of CARG-2020 in solid tumors and demonstrates the potential of CARG-2020 to be developed as a clinical candidate for the treatment of multiple human cancers that are surgically accessible. |
| format | Article |
| id | doaj-art-845dee9eba824db8affefb12db982809 |
| institution | DOAJ |
| issn | 2045-2322 |
| language | English |
| publishDate | 2025-08-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj-art-845dee9eba824db8affefb12db9828092025-08-20T03:04:25ZengNature PortfolioScientific Reports2045-23222025-08-0115111410.1038/s41598-025-14750-1CARG-2020 targets IL-12, IL-17, and PD-L1 pathways to effectively treat melanoma and breast cancerElham Ahmadi0Conner Chiari1Bhaskara Reddy Madina2Timur Olegovich Yarovinsky3Marie Marthe Krady4Ju Chen5Bijan Almassian6Valerian Nakaar7Kepeng Wang8Department of Immunology, School of Medicine, University of Connecticut Health CenterDepartment of Immunology, School of Medicine, University of Connecticut Health CenterCaroGen CorporationCaroGen CorporationCaroGen CorporationDepartment of Immunology, School of Medicine, University of Connecticut Health CenterCaroGen CorporationCaroGen CorporationDepartment of Immunology, School of Medicine, University of Connecticut Health CenterAbstract Cancer immunotherapy has recently achieved a breakthrough status, however, it is not effective in all cancer types. Genetically engineered oncolytic viruses (OVs) with immunomodulators are promising new therapeutic modalities for cancer. CARG-2020 is an engineered trivalent oncolytic viral construct that specifically expresses three immune modulators that inhibit IL-17RA signaling and regulate PD-L1 expression by shRNAs, along with the cytokine IL-12 which activates multiple tumoricidal pathways. Previous work showed that intratumoral (i.t.) injection of CARG-2020 exhibits robust efficacy against established colorectal cancer (CRC). In this study, we report that systemic delivery of CARG-2020 via the intravenous (i.v.) route can successfully control CRC growth. To further expand the scope of CARG-2020 as a pan-cancer candidate, we also show that CARG-2020 works in two additional mouse models of melanoma and triple-negative breast cancer. Administration of CARG-2020 resulted in increased accumulation of CD8+ T lymphocytes in the tumors, and depletion of these T cells results in poor tumor regression mediated by CARG-2020. Overall, our study shows a broad-spectrum efficacy of CARG-2020 in solid tumors and demonstrates the potential of CARG-2020 to be developed as a clinical candidate for the treatment of multiple human cancers that are surgically accessible.https://doi.org/10.1038/s41598-025-14750-1Oncolytic virusCancer immunotherapyInterleukin-12Interleukin-17PD-L1 |
| spellingShingle | Elham Ahmadi Conner Chiari Bhaskara Reddy Madina Timur Olegovich Yarovinsky Marie Marthe Krady Ju Chen Bijan Almassian Valerian Nakaar Kepeng Wang CARG-2020 targets IL-12, IL-17, and PD-L1 pathways to effectively treat melanoma and breast cancer Scientific Reports Oncolytic virus Cancer immunotherapy Interleukin-12 Interleukin-17 PD-L1 |
| title | CARG-2020 targets IL-12, IL-17, and PD-L1 pathways to effectively treat melanoma and breast cancer |
| title_full | CARG-2020 targets IL-12, IL-17, and PD-L1 pathways to effectively treat melanoma and breast cancer |
| title_fullStr | CARG-2020 targets IL-12, IL-17, and PD-L1 pathways to effectively treat melanoma and breast cancer |
| title_full_unstemmed | CARG-2020 targets IL-12, IL-17, and PD-L1 pathways to effectively treat melanoma and breast cancer |
| title_short | CARG-2020 targets IL-12, IL-17, and PD-L1 pathways to effectively treat melanoma and breast cancer |
| title_sort | carg 2020 targets il 12 il 17 and pd l1 pathways to effectively treat melanoma and breast cancer |
| topic | Oncolytic virus Cancer immunotherapy Interleukin-12 Interleukin-17 PD-L1 |
| url | https://doi.org/10.1038/s41598-025-14750-1 |
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