TCR-transgenic T cells and YB-1-based oncolytic virotherapy improve survival in a preclinical Ewing sarcoma xenograft mouse model

• DOI: 10.3389/fimmu.2024.1330868
• Publication Date: 2024-01-22T04:25:40Z
• Authors: Sebastian J. Schober; Melanie Thiede; Hendrik Gassmann; Anna Josefine von...; Pia Knoch; Jennifer Eck; Carolin Prexler; Corazon Kordass-W...; Julia Hauer; Stefan Burdach; Per Sonne Holm; Uwe Thiel
• Keywords: Virotherapy; Oncolytic adenovirus

Background Ewing sarcoma (EwS) is an aggressive and highly metastatic bone soft tissue tumor in pediatric patients young adults. Cure rates are low when present with or relapsed disease. Therefore, innovative therapy approaches urgently needed. Cellular- oncolytic virus-based immunotherapies on the rise for solid cancers. Methods Here, we assess combination of EwS tumor-associated antigen CHM1 319 -specific TCR-transgenic CD8 + T cells YB-1-driven (i.e. E1A13S-deleted) adenovirus XVir-N-31 vitro a xenograft mouse model antitumor activity immunostimulatory properties. Results In both specifically kill cell lines synergistic manner over controls. This effect was confirmed vivo , increased survival using therapy. Further analyses immunogenic death presentation properties virus-infected cells. As dendritic maturation also by XVir-N-31, observed superior proliferation only virus-tested conditions, emphasizing immune-activating potential XVir-N-31. Conclusion Our data prove effects control preclinical setting. Combination strategies EwS-redirected virotherapy promising immunotherapeutic approach warrant further evaluation clinical