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Cancer is the second leading cause of death worldwide, with solid tumors accounting for the majority of cases in adults. Advanced and metastatic solid tumors are responsible for most cancer-related deaths; however, current treatments still fail to achieve both high efficacy and low toxicity. In this study, we constructed an oncolytic virus (OV) named SKM_KK010(h) based on chimpanzee adenovirus serotype 23 (SAdV-23). This OV utilizes an optimized human telomerase reverse transcriptase (hTERT) promoter to drive e1a gene expression, thereby restricting viral replication and oncolysis to tumor cells. Additionally, it carries the csf2 transgene, which encodes human granulocyte-macrophage colony-stimulating factor (GM-CSF), to activate systemic anti-tumor immunity. Experiments in vitro demonstrated that SKM_KK010(h) selectively kills a broad range of tumor cell lines — including colon, bladder, liver, lung, and prostate cancer cells — while exhibiting no cytotoxicity toward normal cells. Viral replication in tumor cells was 100- to 1 000-fold higher than in normal cells. Furthermore, SKM_KK010(h) selectively and efficiently expresses bioactive GM-CSF in the tested tumor cells, reaching a level of 147.60 ± 7.63 ng per 106 cells per 24 h (e.g., in LoVo cells), far exceeding the in vivo efficacy threshold (40 ng per 106 cells per 24 h) required to elicit potent antitumor immunity. In contrast, GM-CSF expressions were undetectable or minimal in normal cells. In a LoVo xenograft mouse model, intratumoral injection of SKM_KK010(h) effectively inhibited tumor growth, achieving a relative tumor proliferation rate (T/C%) of 33.01%. In summary, we have successfully developed a safe and effective oncolytic chimpanzee adenovirus with strong potential as a platform for next-generation oncolytic virotherapy. All animal experiments were approved by the Institutional Ethics Committee and conducted in accordance with relevant ethical guidelines (Ethics Approval Number: IACUC-KYB2301P).
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| 科 Family | 属数 Number of genus | 种数 Number of species | 占总种数比例 Percentage of total species (%) | 属 Genus | 种数 Number of species | 占总种数比例 Percentage of total species (%) |
|---|---|---|---|---|---|---|
| 鹅膏菌科Amanitaceae | 2 | 11 | 5.26 | 鹅膏菌属 Amanita | 10 | 4.78 |
| 小菇科 Mycenaceae | 2 | 12 | 5.74 | 丝盖伞属 Inocybe | 5 | 2.39 |
| 多孔菌科 Polyporaceae | 8 | 14 | 6.70 | 蜡蘑属 Laccaria | 5 | 2.39 |
| 红菇科 Russulaceae | 3 | 23 | 11.00 | 小皮伞属 Marasmius | 6 | 2.87 |
| 小菇属 Mycena | 11 | 5.26 | ||||
| 光柄菇属 Pluteus | 5 | 2.39 | ||||
| 红菇属 Russula | 17 | 8.13 | ||||
| 栓菌属 Trametes | 5 | 2.39 |
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