TY - JOUR
T1 - Safety and efficacy of combined treatment with tumor-infiltrating lymphocytes and oncolytic adenovirus TILT-123 in metastatic melanoma
AU - Monberg, Tine J.
AU - Pakola, Santeri A.
AU - Albieri, Benedetta
AU - Ellebaek, Eva
AU - Donia, Marco
AU - Eefsen, Rikke L.
AU - Borch, Troels H.
AU - Kudling, Tatiana V.
AU - Lorentzen, Torben
AU - Hendel, Helle W.
AU - Vestergaard, Cecilie
AU - Lorentzen, Cathrine
AU - Holmstroem, Rikke B.
AU - Arias, Victor
AU - Khammari, Amir
AU - Kistler, Claudia
AU - Santos, João M.
AU - Clubb, James H.A.
AU - Haybout, Lyna
AU - Westergaard, Marie C.W.
AU - Met, Özcan
AU - Quixabeira, Dafne C.A.
AU - Jirovec, Elise
AU - Havunen, Riikka
AU - Sorsa, Suvi
AU - Cervera-Carrascon, Victor
AU - Dreno, Brigitte
AU - Hemminki, Akseli
AU - Svane, Inge Marie
N1 - Publisher Copyright:
© 2025 The Authors
PY - 2025/3/18
Y1 - 2025/3/18
N2 - 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.
AB - 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.
KW - cancer immunotherapy
KW - combination immunotherapy
KW - cutaneous melanoma
KW - mucosal melanoma
KW - oncolytic virus therapy
KW - TIL therapy
KW - tumor-infiltrating lymphocytes
KW - uveal melanoma
UR - https://www.scopus.com/pages/publications/105000144817
U2 - 10.1016/j.xcrm.2025.102016
DO - 10.1016/j.xcrm.2025.102016
M3 - Journal article
C2 - 40107242
AN - SCOPUS:105000144817
SN - 2666-3791
VL - 6
JO - Cell Reports Medicine
JF - Cell Reports Medicine
IS - 3
M1 - 102016
ER -