Photodynamic augmentation of oncolytic virus therapy for central nervous system malignancies.

Autor: Shimizu K; Department of Neurosurgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA, 02114, USA; Department of Neurosurgery, Tokyo Medical and Dental University, Tokyo, Japan., Kahramanian A; Department of Neurosurgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA, 02114, USA; Department of Neurosurgery, Royal Melbourne Hospital, Melbourne, Australia., Jabbar MADA; Department of Neurosurgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA, 02114, USA., Turna Demir F; Department of Neurosurgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA, 02114, USA; Department of Medical Services and Techniques, Medical Laboratory Techniques Programme, Vocational School of Health Services, Antalya Bilim University, Antalya, Turkey., Gokyer D; Department of Neurosurgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA, 02114, USA., Uthamacumaran A; McGill University, McGill Genome Center, Montreal, Canada; Douglas Mental Health University Institute, Department of Psychiatry, Montreal, Canada., Rajan A; Department of Neurosurgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA, 02114, USA., Saad MA; Wellman Center for Photomedicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA, 02114, USA., Gorham J; Department of Genetics, Harvard Medical School, Boston, MA, 02115, USA., Wakimoto H; Department of Genetics, Harvard Medical School, Boston, MA, 02115, USA., Martuza RL; Department of Neurosurgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA, 02114, USA., Rabkin SD; Department of Neurosurgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA, 02114, USA., Hasan T; Wellman Center for Photomedicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA, 02114, USA; Division of Health Sciences and Technology, Harvard University and Massachusetts Institute of Technology, Cambridge, MA, 02139, USA., Wakimoto H; Department of Neurosurgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA, 02114, USA. Electronic address: hwakimoto@mgh.harvard.edu.
Jazyk: angličtina
Zdroj: Cancer letters [Cancer Lett] 2023 Sep 28; Vol. 572, pp. 216363. Date of Electronic Publication: 2023 Aug 22.
DOI: 10.1016/j.canlet.2023.216363
Abstrakt: Oncolytic viruses (OVs) have emerged as a clinical therapeutic modality potentially effective for cancers that evade conventional therapies, including central nervous system malignancies. Rationally designed combinatorial strategies can augment the efficacy of OVs by boosting tumor-selective cytotoxicity and modulating the tumor microenvironment (TME). Photodynamic therapy (PDT) of cancer not only mediates direct neoplastic cell death but also primes the TME to sensitize the tumor to secondary therapies, allowing for the combination of two potentially synergistic therapies with broader targets. Here, we created G47Δ-KR, clinical oncolytic herpes simplex virus G47Δ that expresses photosensitizer protein KillerRed (KR). Optical properties and cytotoxic effects of G47Δ-KR infection followed by amber LED illumination (peak wavelength: 585-595 nm) were examined in human glioblastoma (GBM) and malignant meningioma (MM) models in vitro. G47Δ-KR infection of tumor cells mediated KR expression that was activated by LED and produced reactive oxygen species, leading to cell death that was more robust than G47Δ-KR without light. In vivo, we tested photodynamic-oncolytic virus (PD-OV) therapy employing intratumoral injection of G47Δ-KR followed by laser light tumor irradiation (wavelength: 585 nm) in GBM and MM xenografts. PD-OV therapy was feasible in these models and resulted in potent anti-tumor effects that were superior to G47Δ-KR alone (without laser light) or laser light alone. RNA sequencing analysis of post-treatment tumor samples revealed PD-OV therapy-induced increases in TME infiltration of variable immune cell types. This study thus demonstrated the proof-of-concept that G47Δ-KR enables PD-OV therapy for neuro-oncological malignancies and warrants further research to advance potential clinical translation.
Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: R.L.M. and S.D.R. are co-inventors on patents relating to oncolytic herpes simplex viruses, owned and managed by Georgetown University and Massachusetts General Hospital (MGH), which have received royalties from Amgen and ActiVec Inc. S.D.R. has received honoraria for expert panel participation from Replimune Inc. All the other authors have no competing interest to declare.
(Copyright © 2023 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
Externí odkaz: