Cytokine-Coding Oncolytic Adenovirus TILT-123 Is Safe, Selective, and Effective as a Single Agent and in Combination with Immune Checkpoint Inhibitor Anti-PD-1

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Havunen , R , Kalliokoski , R , Siurala , M , Sorsa , S , Santos , J M , Cervera-Carrascon , V , Anttila , M & Hemminki , A 2021 , ' Cytokine-Coding Oncolytic Adenovirus TILT-123 Is Safe, Selective, and Effective as a Single Agent and in Combination with Immune Checkpoint Inhibitor Anti-PD-1 ' , Cells , vol. 10 , no. 2 , 246 . https://doi.org/10.3390/cells10020246

Title: Cytokine-Coding Oncolytic Adenovirus TILT-123 Is Safe, Selective, and Effective as a Single Agent and in Combination with Immune Checkpoint Inhibitor Anti-PD-1
Author: Havunen, Riikka; Kalliokoski, Riikka; Siurala, Mikko; Sorsa, Suvi; Santos, Joao M.; Cervera-Carrascon, Victor; Anttila, Marjukka; Hemminki, Akseli
Contributor organization: Medicum
HUS Comprehensive Cancer Center
Department of Oncology
TRIMM - Translational Immunology Research Program
University of Helsinki
Department of Pathology
Research Programs Unit
Date: 2021-02
Language: eng
Number of pages: 16
Belongs to series: Cells
ISSN: 2073-4409
DOI: https://doi.org/10.3390/cells10020246
URI: http://hdl.handle.net/10138/328661
Abstract: 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).
Subject: adenovirus
oncolytic virus
immunotherapy
safety
biodistribution
1182 Biochemistry, cell and molecular biology
Peer reviewed: Yes
Rights: cc_by
Usage restriction: openAccess
Self-archived version: publishedVersion


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