| Autor: |
Heiniö C; Cancer Gene Therapy Group, Faculty of Medicine, TRIMM, RPU, University of Helsinki, 00270 Helsinki, Finland., Clubb J; Cancer Gene Therapy Group, Faculty of Medicine, TRIMM, RPU, University of Helsinki, 00270 Helsinki, Finland.; TILT Biotherapeutics Ltd., 00270 Helsinki, Finland., Kudling T; Cancer Gene Therapy Group, Faculty of Medicine, TRIMM, RPU, University of Helsinki, 00270 Helsinki, Finland., Quixabeira D; Cancer Gene Therapy Group, Faculty of Medicine, TRIMM, RPU, University of Helsinki, 00270 Helsinki, Finland., Cervera-Carrascon V; Cancer Gene Therapy Group, Faculty of Medicine, TRIMM, RPU, University of Helsinki, 00270 Helsinki, Finland.; TILT Biotherapeutics Ltd., 00270 Helsinki, Finland., Havunen R; Cancer Gene Therapy Group, Faculty of Medicine, TRIMM, RPU, University of Helsinki, 00270 Helsinki, Finland.; TILT Biotherapeutics Ltd., 00270 Helsinki, Finland., Grönberg-Vähä-Koskela S; Cancer Gene Therapy Group, Faculty of Medicine, TRIMM, RPU, University of Helsinki, 00270 Helsinki, Finland.; Comprehensive Cancer Center, Helsinki University Hospital, 00270 Helsinki, Finland., Santos JM; Cancer Gene Therapy Group, Faculty of Medicine, TRIMM, RPU, University of Helsinki, 00270 Helsinki, Finland.; TILT Biotherapeutics Ltd., 00270 Helsinki, Finland., Tapper J; Department of Obstetrics and Gynecology, Helsinki University Central Hospital, 00270 Helsinki, Finland., Kanerva A; Department of Obstetrics and Gynecology, Helsinki University Central Hospital, 00270 Helsinki, Finland., Hemminki A; Cancer Gene Therapy Group, Faculty of Medicine, TRIMM, RPU, University of Helsinki, 00270 Helsinki, Finland.; TILT Biotherapeutics Ltd., 00270 Helsinki, Finland.; Comprehensive Cancer Center, Helsinki University Hospital, 00270 Helsinki, Finland. |
| Abstrakt: |
Ovarian cancer (OvCa) is one of the most common gynecological cancers and has the highest mortality in this category. Tumors are often detected late, and unfortunately over 70% of OvCa patients experience relapse after first-line treatments. OvCa has shown low response rates to immune checkpoint inhibitor (ICI) treatments, thus leaving room for improvement. We have shown that oncolytic adenoviral therapy with Ad5/3-E2F-d24-hTNFa-IRES-hIL2 (aka. TILT-123) is promising for single-agent treatment of cancer, but also for sensitizing tumors for T-cell dependent immunotherapy approaches, such as ICI treatments. Therefore, this study set out to determine the effect of inhibition of the immune checkpoint inhibitors (ICI), in the context of TILT-123 therapy of OvCa. We show that simultaneous treatment of patient derived samples with TILT-123 and ICIs anti-PD-1 or anti-PD-L1 efficiently reduced overall viability. The combinations induced T cell activation, T cells expressed activation markers more often, and the treatment caused positive microenvironment changes, measured by flow cytometric assays. Furthermore, in an immunocompetent in vivo C57BL/6NHsda mouse model, tumor growth was hindered, when treated with TILT-123, ICI or both. Taken together, this study provides a rationale for using TILT-123 virotherapy in combination with TILT-123 and immune checkpoint inhibitors together in an ovarian cancer OvCa clinical trial. |
