THER-02. EVALUATION OF THE ONCOLYTIC VIRUS DELTA24-RGD AS AN ANTI-TUMOR AGENT IN PRECLINICAL MODELS OF LOCALIZED AND DISSEMINATED AT/RT

Current therapies for atypical teratoid/rhabdoid tumors (AT/RTs) are suboptimal, resulting in a 2-year OS below 20% and the development of severe side effects. Therefore, we need to explore alternative therapeutic approaches for this disease. Since the virus Delta24-RGD has already demonstrated its efficacy and safety as a therapeutic agent for brain tumors, including pediatric patients, here we propose to evaluate the anti-tumor effect of Delta24-RGD in AT/RT. In vitro, Delta24-RGD infects and replicates in AT/RT cultures followed by oncolysis, obtaining IC(50) values below 1 PFU/cell. In vivo, a single local injection of Delta-24-RGD in three infratentorial AT/RT models (BT-12, CHLA-06 and CHLA-266) extended significantly the median OS (50 to 78 days BT-12; 21 to 31 days CHLA-06; 64 to 110 days CHLA-266). Delta-24-RGD also increased the survival of mice bearing supratentorial CHLA-266 tumors (from 93 to 132 days). Next, we evaluated the efficacy of Delta24-RGD in a model mimicking metastatic disease through intraventricular injection of BT-12-luciferase cells. Administration of Delta24-RGD inhibited tumor growth and development of metastases, leading to an increased OS and nearly 70% of long-term survivors. The interaction between Delta24-RGD and the immune system was evaluated in humanized mice models bearing CHLA-06. In this model, Delta24-RGD treatment extended OS (from 23 to 34 days) and we characterized the anti-tumor immune landscape in control and Delta24-RGD treated mice by transcriptional and functional analyses. These results underscore the potential of Delta24-RGD as a promising therapeutic choice for patients affected by AT/RT.