Safety and efficacy of combined treatment with tumor-infiltrating lymphocytes and oncolytic adenovirus TILT-123 in metastatic melanoma
Tumor-infiltrating lymphocytes (TILs) are effective in the treatment of metastatic melanoma (MM), but toxicity limits its application. TILT-123 (igrelimogene litadenorepvec) is an oncolytic adenovirus producing interleukin-2 (IL-2) and tumor necrosis factor (TNF) upon replication. In this phase 1 trial, 17 patients with metastatic checkpoint inhibitor-resistant melanoma are treated with TILT-123 and TILs without preconditioning chemotherapy or postconditioning IL-2. The treatment is safe and feasible. According to computed tomography (CT), the objective response rate is 11.7% (2/17) and disease control is observed in 35% (6/17), including a partial response lasting >8 months and a durable complete response in a mucosal melanoma patient. According to positron emission tomography (PET), disease control is observed in 7/15 (47%) with minor or partial responses in 4/15 (27%). In the initial TILT-123 monotherapy phase of the trial, disease control is observed in 6/17 (35%) and 10/16 (63%) in CT and PET, respectively. The study demonstrates good tolerability and preliminary efficacy.
Authors
- Brigitte Dréno (ORCID: https://orcid.org/0000-0001-5574-5825)
- Santeri A. Pakola (ORCID: https://orcid.org/0000-0001-6235-8612)
- Rikke B. Holmstroem
- Elise Jirovec (ORCID: https://orcid.org/0009-0004-0606-6577)
- Marco Donia (ORCID: https://orcid.org/0000-0003-4966-9752)
- Tatiana V. Kudling (ORCID: https://orcid.org/0000-0003-4481-1617)
- Riikka Havunen (ORCID: https://orcid.org/0009-0008-7926-5285)
- Eva Ellebæk (ORCID: https://orcid.org/0000-0001-6748-9232)
- Victor Arias (ORCID: https://orcid.org/0000-0002-3631-2896)
- Marie Christine Wulff Westergaard (ORCID: https://orcid.org/0000-0003-3446-4287)
- Benedetta Albieri (ORCID: https://orcid.org/0009-0008-3202-5452)
- James H.A. Clubb (ORCID: https://orcid.org/0000-0002-9146-4817)
- Tine Monberg (ORCID: https://orcid.org/0000-0002-7217-2974)
- Claudia Kistler (ORCID: https://orcid.org/0009-0003-8445-4164)
- Troels Holz Borch (ORCID: https://orcid.org/0000-0002-4402-9281)
- Inge Marie Svane (ORCID: https://orcid.org/0000-0002-9451-6037)
- Lyna Haybout (ORCID: https://orcid.org/0009-0005-5170-5611)
- Dafne C.A. Quixabeira (ORCID: https://orcid.org/0000-0003-2614-3942)
- Cathrine Lund Lorentzen (ORCID: https://orcid.org/0000-0003-2131-2188)
- Christian Vestergaard (ORCID: https://orcid.org/0000-0001-6485-3158)
- Akseli Hemminki (ORCID: https://orcid.org/0000-0001-7103-8530)
- Suvi Sorsa (ORCID: https://orcid.org/0009-0002-1709-611X)
- Amir Khammari
- Rikke Løvendahl Eefsen (ORCID: https://orcid.org/0000-0003-1421-1792)
- Özcan Met (ORCID: https://orcid.org/0000-0002-3256-7592)
- João M. Santos (ORCID: https://orcid.org/0000-0003-4639-1644)
- Helle Westergren Hendel (ORCID: https://orcid.org/0000-0002-6213-0148)
- Víctor Cervera-Carrascón (ORCID: https://orcid.org/0000-0001-6684-3666)
- Torben Lorentzen (ORCID: https://orcid.org/0000-0002-4454-4005)
Institutions
- Centre National de la Recherche Scientifique (FR)
- University of Helsinki (FI)
- Inserm (FR)
- Herlev Hospital (DK)
- Copenhagen University Hospital (DK)
- Biocenter Finland (FI)
- Institute for Molecular Medicine Finland (FI)
- Technical University of Denmark (DK)
- Nantes Université (FR)
Publication Details
- Journal
- Cell Reports Medicine
- Published
- 2025-03-01
- DOI
- https://doi.org/10.1016/j.xcrm.2025.102016
- Citations
- 10
- Primary Topic
- CAR-T cell therapy research
- Type
- article
- Field-Weighted Citation Impact
- 10.45