Boosting anti-tumor immunity with TILT-517 oncolytic adenovirus and checkpoint blockade in renal cell carcinoma
Elevated levels of immune infiltration found in renal cell carcinoma are often associated with poor patient prognosis, likely due to T cell exhaustion and an immunosuppressive tumor microenvironment, which limits the efficacy of current immunotherapies. In this study, we focused on the use of Ad5/3-...
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| Language: | English |
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Elsevier
2025-06-01
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| Series: | Molecular Therapy: Oncology |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2950329925000487 |
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| author | Victor Arias Tatiana V. Kudling James H.A. Clubb Elise Jirovec Santeri A. Pakola Mirte Van der Heijden Saru Basnet Dafne C.A. Quixabeira Lyna Haybout Nea Ojala Susanna Grönberg-Vähä-Koskela Anna Kanerva Antti Rannikko João M. Santos Victor Cervera-Carrascon Otto Hemminki Akseli Hemminki |
| author_facet | Victor Arias Tatiana V. Kudling James H.A. Clubb Elise Jirovec Santeri A. Pakola Mirte Van der Heijden Saru Basnet Dafne C.A. Quixabeira Lyna Haybout Nea Ojala Susanna Grönberg-Vähä-Koskela Anna Kanerva Antti Rannikko João M. Santos Victor Cervera-Carrascon Otto Hemminki Akseli Hemminki |
| author_sort | Victor Arias |
| collection | DOAJ |
| description | Elevated levels of immune infiltration found in renal cell carcinoma are often associated with poor patient prognosis, likely due to T cell exhaustion and an immunosuppressive tumor microenvironment, which limits the efficacy of current immunotherapies. In this study, we focused on the use of Ad5/3-E2F-d24-hIL7 (TILT-517), an oncolytic adenovirus expressing interleukin-7, as a strategy to selectively lyse tumors. This approach also seeks to activate infiltrating immune cells, thereby reprogramming the immune landscape characteristic of renal cell carcinoma tumors. Furthermore, we evaluated the combination of TILT-517 with immune checkpoint inhibitors, main immunotherapeutic component for this disease. Anti-tumor efficacy was significantly observed in ex vivo patient-derived tumors when treated with TILT-517 in monotherapy and in treatment combination. Cellular and proteomic changes were detected in the tumor microenvironment, including enhanced cytotoxicity of effector populations such as CD4+, CD8+ T cells, natural killer, and natural killer T cells. In vivo, we developed a novel syngeneic Syrian hamster model for renal cancer, and TILT-517+anti-PD-L1 group presented significant enhanced tumor growth control and led to an increased number of effector and antigen-presenting cells compared to anti-PD-L1 monotherapy. Hence, TILT-517 offers a promising approach for renal cell carcinoma treatment, boosting therapeutic efficacy and reshaping the tumor microenvironment. |
| format | Article |
| id | doaj-art-2f3fb806bdbe425890bf4fdd5daf81fd |
| institution | OA Journals |
| issn | 2950-3299 |
| language | English |
| publishDate | 2025-06-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Molecular Therapy: Oncology |
| spelling | doaj-art-2f3fb806bdbe425890bf4fdd5daf81fd2025-08-20T02:17:40ZengElsevierMolecular Therapy: Oncology2950-32992025-06-0133220097910.1016/j.omton.2025.200979Boosting anti-tumor immunity with TILT-517 oncolytic adenovirus and checkpoint blockade in renal cell carcinomaVictor Arias0Tatiana V. Kudling1James H.A. Clubb2Elise Jirovec3Santeri A. Pakola4Mirte Van der Heijden5Saru Basnet6Dafne C.A. Quixabeira7Lyna Haybout8Nea Ojala9Susanna Grönberg-Vähä-Koskela10Anna Kanerva11Antti Rannikko12João M. Santos13Victor Cervera-Carrascon14Otto Hemminki15Akseli Hemminki16Cancer Gene Therapy Group, Translational Immunology Research Program, Faculty of Medicine, University of Helsinki, Helsinki, FinlandCancer Gene Therapy Group, Translational Immunology Research Program, Faculty of Medicine, University of Helsinki, Helsinki, FinlandCancer Gene Therapy Group, Translational Immunology Research Program, Faculty of Medicine, University of Helsinki, Helsinki, Finland; TILT Biotherapeutics Ltd, Helsinki, FinlandCancer Gene Therapy Group, Translational Immunology Research Program, Faculty of Medicine, University of Helsinki, Helsinki, FinlandCancer Gene Therapy Group, Translational Immunology Research Program, Faculty of Medicine, University of Helsinki, Helsinki, FinlandCancer Gene Therapy Group, Translational Immunology Research Program, Faculty of Medicine, University of Helsinki, Helsinki, FinlandCancer Gene Therapy Group, Translational Immunology Research Program, Faculty of Medicine, University of Helsinki, Helsinki, FinlandCancer Gene Therapy Group, Translational Immunology Research Program, Faculty of Medicine, University of Helsinki, Helsinki, Finland; TILT Biotherapeutics Ltd, Helsinki, FinlandCancer Gene Therapy Group, Translational Immunology Research Program, Faculty of Medicine, University of Helsinki, Helsinki, Finland; TILT Biotherapeutics Ltd, Helsinki, FinlandCancer Gene Therapy Group, Translational Immunology Research Program, Faculty of Medicine, University of Helsinki, Helsinki, FinlandCancer Gene Therapy Group, Translational Immunology Research Program, Faculty of Medicine, University of Helsinki, Helsinki, Finland; Comprehensive Cancer Center, Helsinki University Hospital (HUS), Helsinki, FinlandCancer Gene Therapy Group, Translational Immunology Research Program, Faculty of Medicine, University of Helsinki, Helsinki, Finland; Department of Obstetrics and Gynecology, Helsinki University Central Hospital (HUS), Helsinki, FinlandDepartment of Urology, Helsinki University Hospital (HUS), Helsinki, Finland; ONCOSYS Research Program in Systems Oncology, Faculty of Medicine, University of Helsinki, Helsinki, FinlandCancer Gene Therapy Group, Translational Immunology Research Program, Faculty of Medicine, University of Helsinki, Helsinki, Finland; TILT Biotherapeutics Ltd, Helsinki, FinlandCancer Gene Therapy Group, Translational Immunology Research Program, Faculty of Medicine, University of Helsinki, Helsinki, Finland; TILT Biotherapeutics Ltd, Helsinki, FinlandCancer Gene Therapy Group, Translational Immunology Research Program, Faculty of Medicine, University of Helsinki, Helsinki, Finland; Department of Urology, Helsinki University Hospital (HUS), Helsinki, FinlandCancer Gene Therapy Group, Translational Immunology Research Program, Faculty of Medicine, University of Helsinki, Helsinki, Finland; TILT Biotherapeutics Ltd, Helsinki, Finland; Comprehensive Cancer Center, Helsinki University Hospital (HUS), Helsinki, Finland; Corresponding author: Prof. Akseli Hemminki, Cancer Gene Therapy Group, Translational Immunology Research Program, Faculty of Medicine, University of Helsinki, Helsinki, FinlandElevated levels of immune infiltration found in renal cell carcinoma are often associated with poor patient prognosis, likely due to T cell exhaustion and an immunosuppressive tumor microenvironment, which limits the efficacy of current immunotherapies. In this study, we focused on the use of Ad5/3-E2F-d24-hIL7 (TILT-517), an oncolytic adenovirus expressing interleukin-7, as a strategy to selectively lyse tumors. This approach also seeks to activate infiltrating immune cells, thereby reprogramming the immune landscape characteristic of renal cell carcinoma tumors. Furthermore, we evaluated the combination of TILT-517 with immune checkpoint inhibitors, main immunotherapeutic component for this disease. Anti-tumor efficacy was significantly observed in ex vivo patient-derived tumors when treated with TILT-517 in monotherapy and in treatment combination. Cellular and proteomic changes were detected in the tumor microenvironment, including enhanced cytotoxicity of effector populations such as CD4+, CD8+ T cells, natural killer, and natural killer T cells. In vivo, we developed a novel syngeneic Syrian hamster model for renal cancer, and TILT-517+anti-PD-L1 group presented significant enhanced tumor growth control and led to an increased number of effector and antigen-presenting cells compared to anti-PD-L1 monotherapy. Hence, TILT-517 offers a promising approach for renal cell carcinoma treatment, boosting therapeutic efficacy and reshaping the tumor microenvironment.http://www.sciencedirect.com/science/article/pii/S2950329925000487MT: regular issueoncolytic virusadenovirusimmunotherapyT cell exhaustioninterleukin 7 |
| spellingShingle | Victor Arias Tatiana V. Kudling James H.A. Clubb Elise Jirovec Santeri A. Pakola Mirte Van der Heijden Saru Basnet Dafne C.A. Quixabeira Lyna Haybout Nea Ojala Susanna Grönberg-Vähä-Koskela Anna Kanerva Antti Rannikko João M. Santos Victor Cervera-Carrascon Otto Hemminki Akseli Hemminki Boosting anti-tumor immunity with TILT-517 oncolytic adenovirus and checkpoint blockade in renal cell carcinoma Molecular Therapy: Oncology MT: regular issue oncolytic virus adenovirus immunotherapy T cell exhaustion interleukin 7 |
| title | Boosting anti-tumor immunity with TILT-517 oncolytic adenovirus and checkpoint blockade in renal cell carcinoma |
| title_full | Boosting anti-tumor immunity with TILT-517 oncolytic adenovirus and checkpoint blockade in renal cell carcinoma |
| title_fullStr | Boosting anti-tumor immunity with TILT-517 oncolytic adenovirus and checkpoint blockade in renal cell carcinoma |
| title_full_unstemmed | Boosting anti-tumor immunity with TILT-517 oncolytic adenovirus and checkpoint blockade in renal cell carcinoma |
| title_short | Boosting anti-tumor immunity with TILT-517 oncolytic adenovirus and checkpoint blockade in renal cell carcinoma |
| title_sort | boosting anti tumor immunity with tilt 517 oncolytic adenovirus and checkpoint blockade in renal cell carcinoma |
| topic | MT: regular issue oncolytic virus adenovirus immunotherapy T cell exhaustion interleukin 7 |
| url | http://www.sciencedirect.com/science/article/pii/S2950329925000487 |
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