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
Open Access
- 27 January 2021
- Vol. 10 (2), 246
- https://doi.org/10.3390/cells10020246
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).Funding Information
- Jane and Aatos Erkko Foundation (N/A, N/A, N/A, N/A, N/A, N/A, N/A, N/A)
This publication has 33 references indexed in Scilit:
- Biodistribution Analysis of Oncolytic Adenoviruses in Patient Autopsy Samples Reveals Vascular Transduction of Noninjected Tumors and TissuesMolecular Therapy, 2015
- A century of oncolysis evolves into oncolytic immunotherapyOncoImmunology, 2015
- Safety and Efficacy of VCN-01, an Oncolytic Adenovirus Combining Fiber HSG-Binding Domain Replacement with RGD and Hyaluronidase ExpressionClinical Cancer Research, 2015
- PD-1 is a novel regulator of human B-cell activationInternational Immunology, 2012
- Desmoglein 2 is a receptor for adenovirus serotypes 3, 7, 11 and 14Nature Medicine, 2010
- Oncolytic Adenovirus Coding for Granulocyte Macrophage Colony-Stimulating Factor Induces Antitumoral Immunity in Cancer PatientsCancer Research, 2010
- A Phase I Study of Telomerase-specific Replication Competent Oncolytic Adenovirus (Telomelysin) for Various Solid TumorsMolecular Therapy, 2010
- INGN 007, an oncolytic adenovirus vector, replicates in Syrian hamsters but not mice: comparison of biodistribution studiesCancer Gene Therapy, 2009
- China Approves World's First Oncolytic Virus Therapy For Cancer TreatmentJNCI Journal of the National Cancer Institute, 2006
- Syrian Hamster as a Permissive Immunocompetent Animal Model for the Study of Oncolytic Adenovirus VectorsCancer Research, 2006