ArticleClinical cancer research : an official journal of the American Association for Cancer Research2016
Bortezomib Treatment Sensitizes Oncolytic HSV-1-Treated Tumors to NK Cell Immunotherapy.
Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 56 papers.
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Who cites it
56 citing papers in PubMed, 86 citations in OpenAlex.
- Heat up and Destroy: Immunotherapy of "Cold" Tumors Using the Example of Glioblastoma.International journal of molecular sciences · 2026Review
- The promise of immunotherapy for central nervous system tumours.Nature reviews. Immunology · 2026Review
- Oncolytic HSV1716 attenuates tumor-killing activity of infected primary NK cells.Frontiers in immunology · 2026Article
- Enhanced oral nanomedicine utilizing biomineralized oncolytic virus for synergistic gastrointestinal cancer therapy.Materials today. Bio · 2025Article
- Oncolytic HSV and cancer drug interactions: Current clinical status and future directions.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Review
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- Proteasome inhibition enhances oncolytic reovirus therapy in multiple myeloma independently of its direct cytotoxic effects.Journal of hematology & oncology · 2025Article
- Viral warfare: unleashing engineered oncolytic viruses to outsmart cancer's defenses.Frontiers in immunology · 2025Review
- Tracing from Periphery to Cortex: Application of Herpes Simplex Virus to Somatosensory Neural Networks.Neuroscience bulletin · 2024Article
- The combination therapy of oncolytic virotherapy.Frontiers in pharmacology · 2024Review
- Oncolytic virotherapy evolved into the fourth generation as tumor immunotherapy.Journal of translational medicine · 2023Review
- Opportunities and challenges of combining adoptive cellular therapy with oncolytic virotherapy.Molecular therapy oncolytics · 2023Review
- Oncolytic virotherapy: basic principles, recent advances and future directions.Signal transduction and targeted therapy · 2023Review
- Advances in NK cell therapy for brain tumors.NPJ precision oncology · 2023Review
- A new approach to overcoming resistance to immunotherapy: nanotechnology.Frontiers in oncology · 2023Review
- Systemic delivery of glycosylated-PEG-masked oncolytic virus enhances targeting of antitumor immuno-virotherapy and modulates T and NK cell infiltration.Theranostics · 2023Article
- Nanomedicines for Overcoming Cancer Drug Resistance.Pharmaceutics · 2022Review
- Cutting both ways: the innate immune response to oncolytic virotherapy.Cancer gene therapy · 2022Review
Corrections and comments
- Erratum issued
Authors and funding
17 authors at 2 institutions in 1 country.
Funding
Abstract
purposeBoth the proteasome inhibitor bortezomib and an oncolytic herpes simplex virus-1 (oHSV)-expressing GM-CSF are currently FDA approved. Although proteasome blockade can increase oHSV replication, immunologic consequences, and consequent immunotherapy potential are unknown. In this study, we investigated the impact of bortezomib combined with oHSV on tumor cell death and sensitivity to natural killer (NK) cell immunotherapy. EXPERIMENTAL
designWestern blot, flow cytometry, and caspase 3/7 activity assays were used to evaluate the induction of apoptosis/autophagy and/or necroptotic cell death. Cellular and mitochondrial reactive oxygen species (ROS) production was measured using CellROX and MitoSOX. Inhibitors/shRNA-targeting ROS, JNK and RIP1 kinase (RIPK1) were used to investigate the mechanism of cell killing. The synergistic interaction between oHSV and bortezomib was calculated using a Chou-Talalay analysis. NK cells isolated from normal human blood were co-cultured with tumor cells to evaluate cellular interactions. Q-PCR, ELISA, and FACS analysis were used to evaluate NK cell activation. Intracranial tumor xenografts were used to evaluate antitumor efficacy.
resultsCombination treatment with bortezomib- and oHSV-induced necroptotic cell death and increased the production of mitochondrial ROS and JNK phosphorylation. Inhibitors/shRNA of RIPK1 and JNK rescued synergistic cell killing. Combination treatment also significantly enhanced NK cell activation and adjuvant NK cell therapy of mice treated with bortezomib and oHSV improved antitumor efficacy.
conclusionsThis study provides a significant rationale for triple combination therapy with bortezomib, oHSV, and NK cells to improve efficacy, in glioblastoma patients. Clin Cancer Res; 22(21); 5265-76. ©2016 AACRSee related commentary by Suryadevara et al., p. 5164.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.