The Current Landscape of Oncolytic Herpes Simplex Viruses as Novel Therapies for Brain Malignancies

Bernstock, Joshua D.; Hoffman, Samantha E.; Chen, Jason; Gupta, Saksham; Kappel, Ari D.; Smith, Timothy R.; Chiocca, E. Antonio

doi:10.3390/v13061158

Cited by 18 publications

(13 citation statements)

References 49 publications

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“…The detargeting-retargeting approach confers cancer-specificity, albeit not absolute since any given TAA exhibits a limited expression in a few off-tumor tissues [ 10 ]. It differs from the broad group of attenuation strategies, which confer cancer-selectivity and are based on deletion or mutation in virulence genes, including the γ 1 34.5 gene [ 12 ], or in genes that contrast the innate and adaptive immune responses [ 13 , 14 ]. The vast majority of oHSVs in clinical trials, and the approved talimogene laherparepvec (also named OncoVEXGM-CSF) were generated by the latter strategy [ 15 , 16 , 17 ].…”

Section: Introductionmentioning

confidence: 99%

Genotype of Immunologically Hot or Cold Tumors Determines the Antitumor Immune Response and Efficacy by Fully Virulent Retargeted oHSV

Gianni

Leoni

Sanapo

et al. 2021

Viruses

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We report on the efficacy of the non-attenuated HER2-retargeted oHSV named R-337 against the immunologically hot CT26-HER2 tumor, and an insight into the basis of the immune protection. Preliminarily, we conducted an RNA immune profiling and immune cell content characterization of CT26-HER2 tumor in comparison to the immunologically cold LLC1-HER2 tumor. CT26-HER2 tumor was implanted into HER2-transgenic BALB/c mice. Hallmarks of R-337 effects were the protection from primary tumor, long-term adaptive vaccination directed to both HER2 and CT26-wt cell neoantigens. The latter effect differentiated R-337 from OncoVEXGM-CSF. As to the basis of the immune protection, R-337 orchestrated several changes to the tumor immune profile, which cumulatively reversed the immunosuppression typical of this tumor (graphical abstract). Thus, Ido1 (inhibitor of T cell anticancer immunity) levels and T regulatory cell infiltration were decreased; Cd40 and Cd27 co-immunostimulatory markers were increased; the IFNγ cascade was activated. Of note was the dampening of IFN-I response, which we attribute to the fact that R-337 is fully equipped with genes that contrast the host innate response. The IFN-I shut-down likely favored viral replication and the expression of the mIL-12 payload, which, in turn, boosted the antitumor response. The results call for a characterization of tumor immune markers to employ oncolytic herpesviruses more precisely.

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Section: Introductionmentioning

confidence: 99%

Genotype of Immunologically Hot or Cold Tumors Determines the Antitumor Immune Response and Efficacy by Fully Virulent Retargeted oHSV

Gianni

Leoni

Sanapo

et al. 2021

Viruses

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“…In some cases, HSV1 can cause severe infection of the brain and liver and/or death, however the rQNestin virus has been modified to replicate only in glioma cells but not in normal, healthy cells [ 181 ]. The UL39 gene encoding the viral ribonucleotide reductase large subunit infected cell protein 6 (ICP6) and both endogenous copies of the gamma34.5 gene that encodes for the RL1 neurovirulence protein infected cell protein 34.5 (ICP34.5) (needed for robust viral growth in an infected cell) are deleted, and one copy of the gamma34.5 gene is reinserted under control of a nestin promoter, which is selectively activated in gliomas [ 182 ]. By inactivating UL39, viral ribonucleotide reductase activity is disrupted, resulting in the inhibition of nucleotide metabolism and viral DNA synthesis in non-dividing, healthy cells but not in dividing cells [ 183 ].…”

Section: Applications Of Nanotechnology In Cancer Therapeuticsmentioning

confidence: 99%

Cancer nanotechnology: current status and perspectives

2021

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Modern medicine has been waging a war on cancer for nearly a century with no tangible end in sight. Cancer treatments have significantly progressed, but the need to increase specificity and decrease systemic toxicities remains. Early diagnosis holds a key to improving prognostic outlook and patient quality of life, and diagnostic tools are on the cusp of a technological revolution. Nanotechnology has steadily expanded into the reaches of cancer chemotherapy, radiotherapy, diagnostics, and imaging, demonstrating the capacity to augment each and advance patient care. Nanomaterials provide an abundance of versatility, functionality, and applications to engineer specifically targeted cancer medicine, accurate early-detection devices, robust imaging modalities, and enhanced radiotherapy adjuvants. This review provides insights into the current clinical and pre-clinical nanotechnological applications for cancer drug therapy, diagnostics, imaging, and radiation therapy.

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“…This is the fourth OV approved worldwide. 5 In addition to the approved OVs, there are currently several OV products that have been tested in phases I–III clinical trials worldwide, from various types of adenoviruses, HSV, coxsackievirus, poxvirus, and reovirus. It has been demonstrated that the cancer cells infected by OVs secrete a large number of cytokines, while the lysed tumor cells release a variety of tumor-associated antigens.…”

Section: Introductionmentioning

confidence: 99%

Triple-serotype chimeric oncolytic adenovirus exerts multiple synergistic mechanisms against solid tumors

et al. 2022

J Immunother Cancer

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BackgroundOncolytic virotherapy has become an important branch of cancer immunotherapy. This study investigated the efficacy of an oncolytic adenovirus (OAV), OncoViron, with synergistic mechanisms in the treatment of multiple solid tumors.MethodsAn OAV, OncoViron, was constructed and investigated by cytological experiments and implanted tumor models of multiple solid tumor cell lines to certify its anticancer efficacy, the synergistic effects of viral oncolysis and transgene anticancer activity of OncoViron, as well as oncolytic virotherapy combined with immunotherapy, were also verified.ResultsThe selective replication of OncoViron mediated high expression of anticancer factors, specifically targeted a variety of solid tumors and significantly inhibited cancer cell proliferation. On a variety of implanted solid tumor models in immunodeficient mice, immunocompetent mice, and humanized mice, OncoViron showed great anticancer effects on its own and in combination with programmed death 1 (PD-1) antibody and chimeric antigen receptor (CAR) T cells. Pathological examination, single-cell sequencing, and spatial transcriptome analysis of animal implanted tumor specimens confirmed that OncoViron significantly altered the gene expression profile of infected cancer cells, not only recruiting a large number of lymphocytes, natural killer cells, and mononuclear macrophages into tumor microenvironment (TME) and activated immune cells, especially T cells but also inducing M1 polarization of macrophages and promoting the release of more immune cytokines, thereby remodeling the TME for coordinating PD-1 antibody or CAR T therapy.ConclusionsThe chimeric OncoViron is a novel broad-spectrum anticancer product with multiple mechanisms of synergistic and potentiated immunotherapy, creating a good opportunity for combined immunotherapy against solid tumors.

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The Current Landscape of Oncolytic Herpes Simplex Viruses as Novel Therapies for Brain Malignancies

Cited by 18 publications

References 49 publications

Genotype of Immunologically Hot or Cold Tumors Determines the Antitumor Immune Response and Efficacy by Fully Virulent Retargeted oHSV

Genotype of Immunologically Hot or Cold Tumors Determines the Antitumor Immune Response and Efficacy by Fully Virulent Retargeted oHSV

Cancer nanotechnology: current status and perspectives

Triple-serotype chimeric oncolytic adenovirus exerts multiple synergistic mechanisms against solid tumors

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