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...
Saved in:
| Main Authors: | , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Nature Portfolio
2025-08-01
|
| Series: | Scientific Reports |
| Subjects: | |
| Online Access: | https://doi.org/10.1038/s41598-025-14750-1 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| Summary: | 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. |
|---|---|
| ISSN: | 2045-2322 |