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Abstract Introduction: Angiogenesis is a critical aspect of cancer growth and metastasis. Consequently, inhibiting angiogenesis has garnered substantial attention in oncology research. JX-594 (pexastimogene devacirpvec; Pexa-Vec®), engineered from the Wyeth vaccine strain, has emerged as an attractive oncolytic virotherapy and demonstrated oncolytic, immunotherapeutic, and tumor vasculature-disrupting capacities. In our previous study, we found that JX-594 reduced the amount of vasculature in gastric tumors using a xenograft mouse model. In the present study, we investigate the effect of JX-594 on tumor vasculature using an in vitro human cell 3D co-culture model of vascularized gastric cancer, to determine if this tool provides improved accuracy in evaluating the mechanism of action and biological activity of JX-594 as compared to traditional animal models. Methods: The Curio-Spheroid chip is a Microphysiological System (MPS) that can grow tumor organoids or spheroids in 3D using physiologically relevant hydrogels and culturing them with other human cell types such as fibroblasts, endothelial cells, and immune cells. We evaluated nine human gastric cancer cell lines (YCC-18, YCC-19, YCC-22, YCC-30, YCC-32, YCC-38, Hs746T, NUGC-3, SNU-620) for their ability to form spheroids and induce angiogenesis inside Curio-Spheroid chips. We selected YCC-32 for the oncolytic virus testing. Serial increases of M. O. I (multiplicity of infection) of JX-594 disrupted the tumor-induced angiogenesis in a dose-dependent manner. Results: JX-594 treatment of the YCC-32 spheroid resulted in decreased levels of Ki-67 and cytopathic effects in a dose-dependent manner inside the Curio-Spheroid MPS system. Angiogenesis was observed surrounding the spheroid when co-cultured with endothelial cells and fibroblasts. JX-594 decreased YCC-32 spheroid-induced angiogenesis in a dose-dependent manner in the vascularized gastric cancer 3D co-culture model. Conclusion: JX-594 had an inhibitory effect on tumor-induced angiogenesis in our vascularized gastric cancer in vitro 3D human cell co-culture model, demonstrating the utility of the platform as a tool to interrogate the effects of an oncolytic virus on both tumor cell killing and tumor-induced angiogenesis. Citation Format: YeLin Kim, Youngsook Song, Yeongmin Choi, Jinhwan Jang, Suryong Kim, Tsung-Li Liu, Kyusuk Baek, Keunhee Oh, Seunghyun Ma, Tae Soo Kim, Woo Sun Kwon, Sanghee Yoo, Jee Hung Kim, Sun Young Rha. Vascularized gastric cancer 3D co-culture model using a microphysiological system as an oncolytic virus testing platform abstract. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts) ; 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84 (6Suppl): Abstract nr 5396.
Kim et al. (Fri,) studied this question.