Academic Journal
Development of the oncolytic virus, CF33, and its derivatives for peritoneal-directed treatment of gastric cancer peritoneal metastases
| العنوان: | Development of the oncolytic virus, CF33, and its derivatives for peritoneal-directed treatment of gastric cancer peritoneal metastases |
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| المؤلفون: | Yang, Annie, Zhang, Zhifang, Chaurasiya, Shyambabu, Park, Anthony K, Jung, Audrey, Lu, Jianming, Kim, Sang-In, Priceman, Saul, Fong, Yuman, Woo, Yanghee |
| المساهمون: | U.S. Department of Defense, City of Hope |
| المصدر: | Journal for ImmunoTherapy of Cancer ; volume 11, issue 4, page e006280 ; ISSN 2051-1426 |
| بيانات النشر: | BMJ |
| سنة النشر: | 2023 |
| الوصف: | 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 We infected six human GC cell lines AGS, MKN-45, MKN-74, KATO III, SNU-1, and SNU-16 with CF33, CF33-GFP, or CF33-hNIS-antiPDL1 at various multiplicities of infection (0.01, 0.1, 1.0, and 10.0), and performed viral proliferation and cytotoxicity assays. We used immunofluorescence imaging and flow cytometric analysis to verify virus-encoded gene expression. We evaluated the antitumor activity of CF33-hNIS-antiPDL1 following IP treatment (3×10 5 pfu × 3 doses) in an SNU-16 human tumor xenograft model using non-invasive bioluminescence imaging. Results CF33-OVs showed dose-dependent infection, replication, and killing of both diffuse and intestinal subtypes of human GC cell lines. Immunofluorescence imaging showed virus-encoded GFP, hNIS, and anti-PD-L1 antibody scFv expression in CF33-OV-infected GC cells. We confirmed GC cell surface PD-L1 blockade by virus-encoded anti-PD-L1 scFv using flow cytometry. In the xenograft model, CF33-hNIS-antiPDL1 (IP; 3×10 5 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 ... |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| DOI: | 10.1136/jitc-2022-006280 |
| الاتاحة: | http://dx.doi.org/10.1136/jitc-2022-006280 https://syndication.highwire.org/content/doi/10.1136/jitc-2022-006280 |
| Rights: | http://creativecommons.org/licenses/by-nc/4.0/ |
| رقم الانضمام: | edsbas.AEACC26F |
| قاعدة البيانات: | BASE |
| DOI: | 10.1136/jitc-2022-006280 |
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