Spondweni Virus Shows Oncolytic Potential in Endometrial Cancer Cells

Endometrial adenocarcinoma accounts for approximately 80% of all endometrial cancers, affecting more than 400,000 women per year. With advanced disease, the 5-year survival rate drops from 81% to 15%. Previously, our laboratory found that Zika virus (ZKV) has promising oncolytic and anti-tumor activities, reducing tumor volume in murine xenograft models of ovarian and endometrial cancer. Spondweni (SPN) is a flavivirus phylogenetically related to but immunologically distinct from ZKV. Like ZKV infection, most human SPN infections are asymptomatic. We hypothesized that SPN would exhibit oncolytic activity like that of ZKV. The endometrial adenocarcinoma cell line HEC-1-A, which was derived from a stage IA endometrial tumor, was selected for infection with three ZKV strains (MR766, ZIKV-A1, and ZIKV A-2) and one SPN strain (SPN A-1). Using viral plaque assays, AlamarBlue™ cell viability assays, and western blots, we examined viral replication in ZKV- and SPN-infected HEC-1-A cells, measuring NS-1 and viral envelope protein expression, and comparing rates of cell death following viral infection. Our data indicated that HEC-1-A cells are more susceptible to SPN than to ZKV. This discovery provides insight into SPN as an oncolytic therapy and opens the door to exploring its use in other cancer types. Citation Format: Catherine Collins, Emily Gearhart, Caroline Finn, Rajarajeshwari Venkataraman, Peter Phelan, Kenneth Alexander. Spondweni virus is highly oncolytic in endometrial carcinoma-derived HEC-1-A cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 219.