The Dilemma of HSV-1 Oncolytic Virus Delivery: The Method Choice and Hurdles

Tang, Guijin; Wang, Dawei; Zhao, Xiangqian; Feng, Zhen; Chen, Qi; Shen, Yangkun

doi:10.3390/ijms24043681

Cited by 12 publications

(5 citation statements)

References 144 publications

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“…These success makes oHSV an ideal candidate for many other clinical trials incorporating transgenic cytokines for various cancer ailments. One major challenge with oHSV is their presence outside the tumor, which could possibly be overcome by increasing their specificity to tumor-specific tropism, increased tumor infiltration, and sustainable anti-tumor activities in the TME could improve the potentiality of oHSV against various cancers [ 209 ].…”

Section: Recent Clinical Trials For Ovtsmentioning

confidence: 99%

Oncolytic Virus Engineering and Utilizations: Cancer Immunotherapy Perspective

Muthukutty

Yoo

2023

Viruses

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Oncolytic viruses have positively impacted cancer immunotherapy over the past 20 years. Both natural and genetically modified viruses have shown promising results in treating various cancers. Various regulatory authorities worldwide have approved four commercial oncolytic viruses, and more are being developed to overcome this limitation and obtain better anti-tumor responses in clinical trials at various stages. Faster advancements in translating research into the commercialization of cancer immunotherapy and a comprehensive understanding of the modification strategies will widen the current knowledge of future technologies related to the development of oncolytic viruses. In this review, we discuss the strategies of virus engineering and the progress of clinical trials to achieve virotherapeutics.

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Section: Recent Clinical Trials For Ovtsmentioning

confidence: 99%

Oncolytic Virus Engineering and Utilizations: Cancer Immunotherapy Perspective

Muthukutty

Yoo

2023

Viruses

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“…In recent years, a lot of OV therapies have been applied to clinical studies in many countries and there is no obvious adverse reaction, indicating that they are fully applicable to tumor patients of different countries and races, which are shown in Table 1 20 . At present, the main ways of OV administration include local administration, intertumoral administration, and intravenous administration, respectively 21 . Local and intertumoral administration can accurately deliver OVs to some superficial tumors but the effect is poor for tumors with distant metastasis 22 .…”

Section: Introductionmentioning

confidence: 99%

“…20 At present, the main ways of OV administration include local administration, intertumoral administration, and intravenous administration, respectively. 21 Local and intertumoral administration can accurately deliver OVs to some superficial tumors but the effect is poor for tumors with distant metastasis. 22 Intravenous administration can reach distant metastatic tumors but there are still some obstacles.…”

mentioning

confidence: 99%

Application of oncolytic virus in tumor therapy

Huang

Guo

Lin

et al. 2023

Journal of Medical Virology

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Oncolytic viruses (OVs) can selectively kill tumor cells without affecting normal cells, as well as activate the innate and adaptive immune systems in patients. Thus, they have been considered as a promising measure for safe and effective cancer treatment. Recently, a few genetically engineered OVs have been developed to further improve the effect of tumor elimination by expressing specific immune regulatory factors and thus enhance the body's antitumor immunity. In addition, the combined therapies of OVs and other immunotherapies have been applied in clinical.Although there are many studies on this hot topic, a comprehensive review is missing on illustrating the mechanisms of tumor clearance by OVs and how to modify engineered OVs to further enhance their antitumor effects. In this study, we provided a review on the mechanisms of immune regulatory factors in OVs. In addition, we reviewed the combined therapies of OVs with other therapies including radiotherapy and CAR-T or TCR-T cell therapy. The review is useful in further generalize the usage of OV in cancer treatment.

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“…Many different approaches are being used to combat obstacles presented to OV therapeutic success brought by exposing the virus to immune cells in the vasculature, such as infection of immune cells as carriers, nanoparticle viral encapsulation, or tumor retargeting on the viral surface to enhance binding affinity to tumor cells. In other cases, injected titers are merely increased, knowing many virus particles will be victims of phagocytosis and will not arrive at the tumor site [ 10 , 11 ]. Interestingly, intramuscular (IM) administration of OVs has not been used as the sole route of administration for the treatment of cancers, even though it is the standard way of delivering vaccines.…”

Section: Introductionmentioning

confidence: 99%

Multiple Administration Routes, Including Intramuscular Injection, of Oncolytic Tanapoxvirus Variants Significantly Regress Human Melanoma Xenografts in BALB/c Nude Mice Reconstituted with Splenocytes from Normal BALB/c Donors

Monaco,

Idris,

Filpi

et al. 2023

Genes

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Human melanoma is the most aggressive form of skin cancer and is responsible for the most deaths of all skin cancers. Localized tumors, and those which have limited spread, have 5-year survival rates of over 90%, with those numbers steadily rising over the past decade. However, metastatic melanomas have a sharp decrease in 5-year survival rates and are still an area of need for new, successful therapies. Immuno-oncolytic viruses (OVs) have emerged as a promising class of immunovirotherapy that can potentially address this disease. The Food and Drug Administration in the United States has approved one oncolytic herpes simplex virus expressing granulocyte-macrophage colony-stimulating factor (Talimogene Laherparepvec) for the treatment of metastatic melanoma, and others could soon follow for this and other cancers. In previous studies, Tanapoxvirus (TPV) recombinants expressing mouse interleukin-2 (mIL-2) and another expressing bacterial flagellin from Salmonella typhimurium (FliC) have demonstrated anti-tumor efficacy in nude mouse models. TPV replicates only in humans and monkeys, including tumor cells, which makes the use of syngeneic tumor models impossible for the study of this OV in a standard immunocompetent system. In this study, TPV/Δ66R/mIL-2 and TPV/Δ2L/Δ66R/FliC were tested for their ability to treat human melanoma xenografts (SK-MEL3) in a BALB/c nude mouse model reconstituted with splenocytes from genetically compatible, normal BALB/c donor mice. Two SK-MEL3 tumors were transplanted into each flank of BALB/c nude mice, and the larger tumor was treated intratumorally (IT) with virus or mock injection. In one set of animals, mice received adoptive transfers of splenocytes from BALB/c mice on day 4 to reconstitute their immune systems and allow for adaptive immune responses to occur in a xenograft model. Direct IT injection of TPV/Δ66R/mIL-2 led to significantly greater rates of tumor regression compared to reconstituted control (RC) mice in the primary and distant tumor sites, whereas TPV/Δ2L/Δ66R/FliC treatment led to significantly greater rates of tumor regression in distant tumor sites only. A second experiment used TPV/Δ66R/mIL-2 to test whether TPV could be administered intravenously (IV), intramuscularly (IM), or both routes simultaneously to exert similar anti-tumor effects in an indirectly treated tumor. A single SK-MEL3 tumor was transplanted into one flank of BALB/c nude mice and was treated either into the tail vein, the nearest rear leg to the tumor, or both. All mice then received adoptive transfers of splenocytes in the same way as previously described on day 4 and received an additional TPV treatment on day 14. The results demonstrated that TPV/Δ66R/mIL-2 treatment IV or IM had significantly greater rates of tumor regression than RC-treated mice but failed to exert this effect when both routes were used simultaneously. Data obtained through these experiments support the continued development of Tanapoxvirus for the treatment of human melanoma and using immune reconstitution to create intact adaptive immunity in a xenograft context, which can allow other tropism-limited OVs to be studied against human cancers.

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The Dilemma of HSV-1 Oncolytic Virus Delivery: The Method Choice and Hurdles

Cited by 12 publications

References 144 publications

Oncolytic Virus Engineering and Utilizations: Cancer Immunotherapy Perspective

Oncolytic Virus Engineering and Utilizations: Cancer Immunotherapy Perspective

Application of oncolytic virus in tumor therapy

Multiple Administration Routes, Including Intramuscular Injection, of Oncolytic Tanapoxvirus Variants Significantly Regress Human Melanoma Xenografts in BALB/c Nude Mice Reconstituted with Splenocytes from Normal BALB/c Donors

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