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BACKGROUND: Gastric cancer (GC) that metastasizes to the peritoneum is fatal. CF33 and its genetically modified derivatives show cancer selectivity and oncolytic potency against various solid tumors. CF33-hNIS and CF33-hNIS-antiPDL1 have entered phase I trials for intratumoral and intravenous treatments of unresectable solid tumors (NCT05346484) and triple-negative breast cancer (NCT05081492). Here, we investigated the antitumor activity of CF33-oncolytic viruses (OVs) against GC and CF33-hNIS-antiPDL1 in the intraperitoneal (IP) treatment of GC peritoneal metastases (GCPM). METHODS: pfu × 3 doses) in an SNU-16 human tumor xenograft model using non-invasive bioluminescence imaging. RESULTS: pfu × 3 doses) treatment significantly reduced peritoneal tumors (p<0.0001), decreased amount of ascites (62.5% PBS vs 25% CF33-hNIS-antiPDL1) and prolonged animal survival. At day 91, seven out of eight mice were alive in the virus-treated group versus one out of eight in the control group (p<0.01). CONCLUSIONS: Our results show that CF33-OVs can deliver functional proteins and demonstrate effective antitumor activity in GCPM models when delivered intraperitoneally. These preclinical results will inform the design of future peritoneal-directed therapy in GCPM patients.
Yang et al. (Sat,) studied this question.