A1 Vertaisarvioitu alkuperäisartikkeli tieteellisessä lehdessä
Fully intravenous split-dose administration of the oncolytic adenovirus TILT-123 in advanced solid tumors; 
Tekijät: Jirovec, Elise; Jalkanen, Katriina J.; Quixabeira, Dafne C.A.; Clubb, James H.A.; Alanko, Tuomo; Kudling, Tatiana V.; Arias, Victor; Pakola, Santeri A.; Grönberg-Vähä-Koskela, Susanna; van der Heijden, Mirte; Färkkilä, Anniina; Kononen, Juha; Sormunen, Jorma; Kemppainen, Jukka; Hellesuo, Maria; Haybout, Lyna; Kistler, Claudia; Sorsa, Suvi; Havunen, Riikka; Santos, Joao M.; Kanerva, Anna; Cervera-Carrascon, Victor; Hemminki, Otto; Hemminki, Akseli
Kustantaja: Elsevier BV
Julkaisuvuosi: 2026
Lehti: Molecular Therapy
Vuosikerta: 34
Numero: 8
Aloitussivu: 4670
Lopetussivu: 4686
ISSN: 1525-0016
eISSN: 1525-0024
DOI: https://doi.org/10.1016/j.ymthe.2026.05.007
Julkaisun avoimuus kirjaamishetkellä: Avoimesti saatavilla
Julkaisukanavan avoimuus : Osittain avoin julkaisukanava
Verkko-osoite: https://doi.org/10.1016/j.ymthe.2026.05.007
Rinnakkaistallenteen osoite: https://research.utu.fi/converis/portal/detail/Publication/526492462
Rinnakkaistallenteen lisenssi: CC BY
Rinnakkaistallennetun julkaisun versio: Kustantajan versio
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.
Avainsanat:
interleukin-2, Intravenous delivery, oncolytic adenovirus, solid tumors, split-dosing, tumor necrosis factor
Ladattava julkaisu This is an electronic reprint of the original article. |  |
Julkaisussa olevat rahoitustiedot:
This study was supported by the Jane and Aatos Erkko Foundation, TILT Biotherapeutics Oy, the Academy of Finland, HUCH Research Funds (VTR), Cancer Foundation Finland, the Sigrid Juselius Foundation, and the Finnish Red Cross Blood Service.
