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| 논문명 |
Oncolytic adenovirus co-expressing IL-12 and shVEGF potentiates immune checkpoint blockade for treatment of renal cell carcinoma: in vitro, organ-on-a-chip, and in vivo evaluation. |
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| 학술지명 |
Molecular Medicine |
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| 공동저자 |
Choi J, Yun CO, Maeng S, Kim Y, Park E, Yi J, Choi SY, Chang IH, Yoon AR. |
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| 논문구분 |
SCI |
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| 논문번호 |
10.1186/s10020-026-01535-z |
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| 게재년월 |
2026.06 |
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| 사이트URL |
pubmed.ncbi.nlm.nih.gov/42363059/ |
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| Impact Factor |
8.3 |
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| Renal cell carcinoma (RCC) has been known as highly malignant and resistant to standard therapy due to its immunosuppressive tumor microenvironment and aberrant VEGF-mediated angiogenesis. To overcome these therapeutic limitations, here we assessed the therapeutic efficacy of an oncolytic adenovirus (oAd) co-expressing Interleukin-12 (IL-12) and a short hairpin RNA against VEGF (shVEGF) in combination with immune checkpoint inhibitors (ICIs). The oAd/IL12/shVEGF induced RCC-specific cancer cell death in vitro and 3D bioprinted model, leading to greater anti-tumor effect compared with oAd-GMCSF. Furthermore, it potentiates anti-tumor efficacy in RCC orthotopic tumor model. The potent antitumor effect induced by combination of oAd/IL12/shVEGF with anti-PD1 was due to CD4 + or CD8 + T cell- or NK cell-mediated antitumor immune response and effective inhibition of tumor-associated neovascularization. Collectively, oAd/IL12/shVEGF can be a potent strategy to overcome current limitations in conventional RCC therapy by converting the cold tumor microenvironment to an inflamed state to sensitize refractory tumors to ICIs. |
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