| Autor: |
Havunen R; TILT Biotherapeutics Ltd., 00290 Helsinki, Finland.; Cancer Gene Therapy Group, Translational Immunology Research Program and Department of Oncology, University of Helsinki, 00290 Helsinki, Finland., Kalliokoski R; TILT Biotherapeutics Ltd., 00290 Helsinki, Finland., Siurala M; TILT Biotherapeutics Ltd., 00290 Helsinki, Finland., Sorsa S; TILT Biotherapeutics Ltd., 00290 Helsinki, Finland.; Cancer Gene Therapy Group, Translational Immunology Research Program and Department of Oncology, University of Helsinki, 00290 Helsinki, Finland., Santos JM; TILT Biotherapeutics Ltd., 00290 Helsinki, Finland.; Cancer Gene Therapy Group, Translational Immunology Research Program and Department of Oncology, University of Helsinki, 00290 Helsinki, Finland., Cervera-Carrascon V; TILT Biotherapeutics Ltd., 00290 Helsinki, Finland.; Cancer Gene Therapy Group, Translational Immunology Research Program and Department of Oncology, University of Helsinki, 00290 Helsinki, Finland., Anttila M; Pathology Unit, Finnish Food Authority, 00790 Helsinki, Finland., Hemminki A; TILT Biotherapeutics Ltd., 00290 Helsinki, Finland.; Cancer Gene Therapy Group, Translational Immunology Research Program and Department of Oncology, University of Helsinki, 00290 Helsinki, Finland.; Helsinki University Hospital Comprehensive Cancer Center, 00290 Helsinki, Finland. |
| Abstrakt: |
Oncolytic viruses provide a biologically multi-faceted treatment option for patients who cannot be cured with currently available treatment options. We constructed an oncolytic adenovirus, TILT-123, to support T-cell therapies and immune checkpoint inhibitors in solid tumors. Adenoviruses are immunogenic by nature, are easy to produce in large quantities, and can carry relatively large transgenes. They are the most commonly used gene therapy vectors and are well tolerated in patients. TILT-123 expresses two potent cytokines, tumor necrosis factor alpha and interleukin-2, to stimulate especially the T-cell compartment in the tumor microenvironment. Before entering clinical studies, the safety and biodistribution of TILT-123 was studied in Syrian hamsters and in mice. The results show that TILT-123 is safe in animals as monotherapy and in combination with an immune checkpoint inhibitor anti-PD-1. The virus treatment induces acute changes in circulating immune cell compartments, but the levels return to normal by the middle of the treatment period. The virus is rapidly cleared from healthy tissues, and it does not cause damage to vital organs. The results support the initiation of a phase 1 dose-escalation trial, where melanoma patients receiving a tumor-infiltrating lymphocyte therapy are treated with TILT-123 (NCT04217473). |
