Abstract Background: Oncolytic viruses represent a promising therapeutic approach through their dual mechanisms of direct tumor cell lysis and stimulation of anti-tumour immunity. IVX055 is a novel, non-enveloped, single-stranded RNA oncolytic virus developed using a proprietary receptor bio-selection platform, which enables preferential targeting of tumor cells by exploiting overexpressed surface receptors. This platform enhances tumor specificity, efficient viral entry, and replication within the tumor microenvironment. Infection with IVX055 induces cell lysis and potential pro-inflammatory signaling, including PD-L1 upregulation, which may increase immune cell infiltration and sensitize tumors to immune checkpoint inhibitors (ICIs). These immunostimulatory effects position IVX055 as a strong candidate for combination with ICIs, T-cell engagers, antibody-drug conjugates (ADCs), and bispecific antibodies to amplify anti-tumor responses. Methods: The oncolytic activity of IVX055 was evaluated in vitro using multiple human Non-small cell lung cancer (NSCLC), hepatocellular carcinoma (HCC) and bladder cancer cell lines. Monolayer cultures were infected with varying multiplicities of infection (MOIs). Cell viability was measured using the XTT assay as a surrogate for cytolytic activity and metabolic function. For mouse models, immunocompromized mice were seeded with single flank human tumor cell administrations. Following development of palpable tumors, IVX055 was administered via the i.t route. calliper measurements were employed to assess tumor burden. Results: IVX055 demonstrated potent, dose-dependent cytolytic activity in NSCLC, HCC and bladder cancer cell lines. Multiple rounds of viral replication were evident, consistent with high level production of progeny virus coupled with sustained oncolytic activity and induction of a potential pro-inflammatory tumour phenotype. Significant reductions in cell viability were detected shortly after infection, confirming rapid and robust tumor cell killing. Intratumoral administration of IVX055 in human tumor xenograft models using immunocompromized mice was well tolerated and displayed potent anti-tumor activity against NSCLC cancers. Conclusions: IVX055 exhibits strong preclinical in vitro and in vivo oncolytic activity and tumor selectivity, supporting its continued development. Future studies will explore combination strategies with ICIs, T-cell engagers, ADCs, and bispecific antibodies to enhance efficacy in advanced solid tumours. A phase 1 basket study of intratumoral IVX055 in combination with systemic anti-PD1 therapy in pts (n=32) bearing visceral disease from checkpoint refractory NSCLC, HCC and Cholangiocarcinoma is planned to commence in 2026. Citation Format: Min Quah, Christine Lee, Rebecca Ingham, Oksana Zdanska, Darren Shafren. High affinity receptor bio-selected novel oncolytic RNA virus, IVX055, demonstrates potent anti-tumor activity in human NSCLC, hepatocellular carcinoma and bladder cancer with potential for immunotherapeutic combinations 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 4377.
Quah et al. (Fri,) studied this question.