PACM-04 ONCOLYTIC ADENOVIRUS RGDOX INDUCES SYSTEMIC CD8+ T CELL–MEDIATED IMMUNITY ACROSS INTRACRANIAL MELANOMA METASTASES: RATIONALE FOR A PHASE I TRIAL

作者：Yi Du, Sanjay Singh, Alejandra Duran, Xizi Wu, Chibawanye Ene, Joy Gumin, Hong Jiang, Dong Ho Shin, Xuejun Fan, David Peng, Javier Gomez, Manu Sebastian, Naema Nayyar, Priscilla Brastianos, Hussein Tawbi, Michael Davies, Frederick Lang, Candelaria Gomez‐Manzano, Juàn Fueyo, Christopher Alvarez-Breckenridge · 发表于：Neuro-Oncology Advances · 年份：2026 · DOI：10.1093/noajnl/vdag161.069 · 研究领域：Virus-based gene therapy research、CAR-T cell therapy research、Glioma Diagnosis and Treatment

Abstract Amongst solid cancers, melanoma brain metastases (MBM) have the highest likelihood of metastasizing to the brain. The use of immune checkpoint inhibitors (ICI) has emerged as first line therapy; however, intracranial progression and acquired resistance highlight the need for novel immunotherapeutic strategies for this patient population. Oncolytic viral (OV) therapy leverages tumor cell replication machinery to selectively replicate and kill tumor cells while promoting anti-tumor immunity. The oncolytic adenovirus Delta-24-RGDOX (RGDOX) has been shown to function as a TME modulator in both preclinical and clinical settings. Here, we investigated the anti-tumor efficacy of RGDOX combined with ICIs in synchronous extracranial—intracranial (s.c.-i.c.) and intracranial—intracranial (i.c.-i.c.) murine melanoma models (B16F10 and D4M). Using this approach, we inoculated the s.c. (s.c.-i.c. model) or i.c. (i.c.-i.c.) tumor with RGDOX and monitored for viral induced cytotoxicity within the infected tumor while assessing for the simultaneous generation of intracranial antitumor immunity against the uninfected tumor. The combinatorial strategy of RGDOX with PD-1/CTLA-4 inhibition significantly reduced tumor growth within the infected and distant intracranial tumor while also improving survival in tumor bearing mice. Through a series of immune depletion experiments, therapeutic efficacy was determined to be mediated through CD8+ T cells. Additionally, eradication of subcutaneou...