Academic Journal
Fully intravenous split-dose administration of the oncolytic adenovirus TILT-123 in advanced solid tumors.
| Title: | Fully intravenous split-dose administration of the oncolytic adenovirus TILT-123 in advanced solid tumors. |
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| Authors: | Jirovec E; Cancer Gene Therapy Group, Translational Immunology Research Program, University of Helsinki, Helsinki, Finland., Jalkanen KJ; Comprehensive Cancer Center, HUS Helsinki University Hospital, Helsinki, Finland., Quixabeira DCA; Cancer Gene Therapy Group, Translational Immunology Research Program, University of Helsinki, Helsinki, Finland; TILT Biotherapeutics Oy, Helsinki, Finland., Clubb JHA; Cancer Gene Therapy Group, Translational Immunology Research Program, University of Helsinki, Helsinki, Finland; TILT Biotherapeutics Oy, Helsinki, Finland., Alanko T; Docrates Cancer Center, Helsinki, Finland., Kudling TV; Cancer Gene Therapy Group, Translational Immunology Research Program, University of Helsinki, Helsinki, Finland; TILT Biotherapeutics Oy, Helsinki, Finland., Arias V; Cancer Gene Therapy Group, Translational Immunology Research Program, University of Helsinki, Helsinki, Finland., Pakola SA; Cancer Gene Therapy Group, Translational Immunology Research Program, University of Helsinki, Helsinki, Finland., Grönberg-Vähä-Koskela S; Cancer Gene Therapy Group, Translational Immunology Research Program, University of Helsinki, Helsinki, Finland; Comprehensive Cancer Center, HUS Helsinki University Hospital, Helsinki, Finland., van der Heijden M; Cancer Gene Therapy Group, Translational Immunology Research Program, University of Helsinki, Helsinki, Finland., Färkkilä A; Research Programs in Systems Oncology, Faculty of Medicine, University of Helsinki, Helsinki, Finland; Institute for Molecular Medicine Finland, Helsinki Institute Sciences, University of Helsinki, Helsinki, Finland; Clinical Trials Unit, Department of Oncology & Department of Obstetrics and Gynecology, Helsinki University Hospital, Helsinki, Finland., Kononen J; Docrates Cancer Center, Helsinki, Finland., Sormunen J; Docrates Cancer Center, Helsinki, Finland., Kemppainen J; Docrates Cancer Center, Helsinki, Finland; Department of Clinical Physiology and Nuclear Medicine, Turku University Hospital, Turku, Finland., Hellesuo M; Docrates Cancer Center, Helsinki, Finland., Haybout L; Cancer Gene Therapy Group, Translational Immunology Research Program, University of Helsinki, Helsinki, Finland; TILT Biotherapeutics Oy, Helsinki, Finland., Kistler C; TILT Biotherapeutics Oy, Helsinki, Finland., Sorsa S; Cancer Gene Therapy Group, Translational Immunology Research Program, University of Helsinki, Helsinki, Finland; TILT Biotherapeutics Oy, Helsinki, Finland., Havunen R; Cancer Gene Therapy Group, Translational Immunology Research Program, University of Helsinki, Helsinki, Finland; TILT Biotherapeutics Oy, Helsinki, Finland., Santos JM; Cancer Gene Therapy Group, Translational Immunology Research Program, University of Helsinki, Helsinki, Finland; TILT Biotherapeutics Oy, Helsinki, Finland., Kanerva A; Cancer Gene Therapy Group, Translational Immunology Research Program, University of Helsinki, Helsinki, Finland; Department of Gynecology and Obstetrics, Helsinki University Hospital, Helsinki, Finland., Cervera-Carrascon V; Cancer Gene Therapy Group, Translational Immunology Research Program, University of Helsinki, Helsinki, Finland; TILT Biotherapeutics Oy, Helsinki, Finland., Hemminki O; Cancer Gene Therapy Group, Translational Immunology Research Program, University of Helsinki, Helsinki, Finland; Department of Urology, Helsinki University Hospital, Helsinki, Finland., Hemminki A; Cancer Gene Therapy Group, Translational Immunology Research Program, University of Helsinki, Helsinki, Finland; Comprehensive Cancer Center, HUS Helsinki University Hospital, Helsinki, Finland; TILT Biotherapeutics Oy, Helsinki, Finland. Electronic address: akseli.hemminki@helsinki.fi. |
| Source: | Molecular therapy : the journal of the American Society of Gene Therapy [Mol Ther] 2026 Aug 05; Vol. 34 (8), pp. 4670-4686. Date of Electronic Publication: 2026 May 13. |
| Publication Type: | Journal Article; Clinical Trial, Phase I |
| Language: | English |
| Journal Info: | Publisher: Cell Press Country of Publication: United States NLM ID: 100890581 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1525-0024 (Electronic) Linking ISSN: 15250016 NLM ISO Abbreviation: Mol Ther Subsets: MEDLINE |
| Imprint Name(s): | Publication: 2017- : Cambridge, MA : Cell Press Original Publication: San Diego, CA : Academic Press, 2000- |
| MeSH Terms: | Adenoviridae*/genetics , Oncolytic Viruses*/genetics , Neoplasms*/therapy , Neoplasms*/mortality , Neoplasms*/pathology , Neoplasms*/genetics , Oncolytic Virotherapy*/methods , Oncolytic Virotherapy*/adverse effects , Genetic Vectors*/administration & dosage , Genetic Vectors*/genetics, Interleukin-2/genetics ; Tumor Necrosis Factor-alpha/genetics ; Humans ; Female ; Male ; Middle Aged ; Aged ; Treatment Outcome ; Administration, Intravenous ; Positron Emission Tomography Computed Tomography ; Adult |
| Abstract: | TILT-123 (Ad5/3-E2F-d24-hTNFα-IRES-hIL2, igrelimogene litadenorepvec) is a chimeric oncolytic adenovirus engineered to selectively replicate in tumor cells and express tumor necrosis factor (TNF) and interleukin-2 (IL-2). While oncolytic viruses are commonly administered intratumorally, this approach often restricts practical applicability. Intravenous delivery is less invasive and offers a more practical alternative; however, systemic immune barriers challenge effective tumor targeting. In a cohort of a phase 1 clinical trial, six patients with advanced solid tumors who had exhausted standard treatments received two intravenous doses of TILT-123 (split-dose), per treatment day across seven cycles. Safety was the primary objective, while efficacy outcomes were exploratory and assessed using positron emission tomography/-computed tomography (PET/CT) imaging, along with overall survival. Split-dosing was safe, with chills, fever, fatigue, and lymphocyte reduction being the most common treatment-related events. In imaging, the disease control rate was 83.3% according to PET criteria and 33.3% by RECIST 1.1. The median overall survival was 198 days. Split-dosing increased the area under the curve of TILT-123 and amplified systemic cytokine responses. Proteomic analysis of serum and neutralizing antibody profiling indicated that enhanced humoral immune activity was associated with shorter overall survival. Post-treatment biopsies confirmed virus presence and alterations in immune cell composition. These findings support further evaluation of intravenous TILT-123 administration in clinical trials. (Copyright © 2026 The Author(s). Published by Elsevier Inc. All rights reserved.) |
| Competing Interests: | Declaration of interests A.H. is a shareholder in Circio Holdings ASA. A.H., V.C.-C., J.H.A.C., and C.K. are employees of and shareholders in TILT Biotherapeutics Oy. O.H. is a shareholder in TILT Biotherapeutics Oy. L.H., D.C.A.Q., R.H., T.V.K., and S.S. are employees of TILT Biotherapeutics. J.M.S. is a TILT Biotherapeutics Oy shareholder, and at the time of the study, he was an employee of TILT Biotherapeutics Oy. K.J.J. has held advisory roles (Bayer AG, Bristol-Myers Squibb, MSD, Roche, Ipsen) and is a shareholder in Faron Pharmaceuticals. |
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| Contributed Indexing: | Keywords: immunotherapy; interleukin-2; intravenous delivery; oncolytic adenovirus; solid tumors; split-dosing; tumor necrosis factor |
| Substance Nomenclature: | 0 (Interleukin-2) 0 (Tumor Necrosis Factor-alpha) |
| Entry Date(s): | Date Created: 20260515 Date Completed: 20260805 Latest Revision: 20260926 |
| Update Code: | 20260926 |
| PubMed Central ID: | PMC13464138 |
| DOI: | 10.1016/j.ymthe.2026.05.007 |
| PMID: | 42136030 |
| Database: | MEDLINE |
| ISSN: | 1525-0024 |
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| DOI: | 10.1016/j.ymthe.2026.05.007 |