Abstract 280: Delta-24-RGDOX: Making Cancer More “visible” to the Immune System

Abstract Emerging evidence indicates that host immunity is critical for successful cancer virotherapy. We found that oncolytic adenovirus Delta-24-RGD elicited antiglioma immunity in an immunocompetent murine model. Recent studies suggested that the therapeutic efficacy of immune checkpoint blockade in cancer patients could be enhanced by strategies inducing tumor inflammation. We hypothesized that highly immunogenic adenovirus combined with targeting immune co-stimulator would result in better anti-tumor efficiency. Thus, we used the backbone of Delta-24-RGD to express the mouse OX40 ligand to increase the recognition of tumor-associated antigens by immune cells. The resulting Delta-24-RGDOX adenovirus maintained the oncolytic potency of Delta-24-RGD and efficiently expressed OX40 ligand on infected cells. More importantly, compared to Delta-24-RGD, Delta-24-RGDOX induced higher antiglioma activity in immunocompetent glioma models but not in an immunodeficient model, and accordingly mediated greater lymphocyte infiltration at tumor sites and stronger lymphocyte antitumor activity. While blocking or stimulating immune checkpoints with antibodies currently dominates the clinical applications, our data demonstrate that intratumoral injection of oncolyticviruses carrying immune co-stimulatory ligands may constitute a powerful alternative to the use of antibodies and other strategies targeting immune checkpoints in cancer therapy. Note: This abstract was not presented at the meeting. Citation Format: Hong Jiang, Xuejun Fan, Karen Clise-Dwyer, Laura Bover, Joy Gumin, Kathryn E. Ruisaard, Farah J. Mukheef, Frederick F. Lang, Candelaria Gomez-Manzano, Juan Fueyo. Delta-24-RGDOX: making cancer more “visible” to the immune system. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 280. doi:10.1158/1538-7445.AM2015-280