Perspectives for Combining Viral Oncolysis With Additional Immunotherapies for the Treatment of Melanoma

Cerqueira, Otto Luiz Dutra; Antunes, Fernanda; Assis, Nadine G; Cardoso, Elizabeth; Clavijo-Salomon, Maria Alejandra; Domingues, Ana Carolina M; Tessarollo, Nayara G.; Strauss, Bryan E.

doi:10.3389/fmolb.2022.777775

Cited by 3 publications

(3 citation statements)

References 235 publications

(289 reference statements)

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“…Intratumoral administration of the oncolytic poliovirus PVSRIPO, the live attenuated, type I poliovirus (Sabin) vaccine harboring an internal ribosome entry site (IRES) of human rhinovirus type 2, has demonstrated initial promise in patients with recurrent glioblastoma multiforme (NCT03712358) ( 110 ). In contrast, PVSRIPO infects macrophages and DCs in culture, causing the expression of major histocompatibility complex class II (MHC II) and the generation of IFN-b and IL-12 ( 9 , 87 ).…”

Section: Various Types Of Ovsmentioning

confidence: 99%

“…Currently, oncolytic virotherapy (OVT) is one of the most popular cancer immunotherapy approaches owing to the flexibility of viral production platforms and providing a multimodal strategy to selectively and efficiently target and destroy tumor cells ( 9 , 10 ). Furthermore, OV platforms could be applied without depth knowledge of tumor antigens in various malignancies ( 11 ).…”

Section: Introductionmentioning

confidence: 99%

“…Newer methods, like combining OVs with immunotherapies to turn “immune-cold” tumors into “immune-hot” ones, can almost certainly make OVs more effective ( 3 , 15 , 16 ). The use of rational combination therapies and targeting have been raised to improve the efficacy of OVs, and these combinations may integrate multiple methodologies and technologies that can increase patient benefit from the treatment ( 9 , 17 ).…”

Section: Introductionmentioning

confidence: 99%

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Immunovirotherapy: The role of antibody based therapeutics combination with oncolytic viruses

Jafari

Kadkhodazadeh²,

Shapourabadi³

et al. 2022

Front. Immunol.

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Despite the fact that the new drugs and targeted therapies have been approved for cancer therapy during the past 30 years, the majority of cancer types are still remain challenging to be treated. Due to the tumor heterogeneity, immune system evasion and the complex interaction between the tumor microenvironment and immune cells, the great majority of malignancies need multimodal therapy. Unfortunately, tumors frequently develop treatment resistance, so it is important to have a variety of therapeutic choices available for the treatment of neoplastic diseases. Immunotherapy has lately shown clinical responses in malignancies with unfavorable outcomes. Oncolytic virus (OV) immunotherapy is a cancer treatment strategy that employs naturally occurring or genetically-modified viruses that multiply preferentially within cancer cells. OVs have the ability to not only induce oncolysis but also activate cells of the immune system, which in turn activates innate and adaptive anticancer responses. Despite the fact that OVs were translated into clinical trials, with T-VECs receiving FDA approval for melanoma, their use in fighting cancer faced some challenges, including off-target side effects, immune system clearance, non-specific uptake, and intratumoral spread of OVs in solid tumors. Although various strategies have been used to overcome the challenges, these strategies have not provided promising outcomes in monotherapy with OVs. In this situation, it is increasingly common to use rational combinations of immunotherapies to improve patient benefit. With the development of other aspects of cancer immunotherapy strategies, combinational therapy has been proposed to improve the anti-tumor activities of OVs. In this regard, OVs were combined with other biotherapeutic platforms, including various forms of antibodies, nanobodies, chimeric antigen receptor (CAR) T cells, and dendritic cells, to reduce the side effects of OVs and enhance their efficacy. This article reviews the promising outcomes of OVs in cancer therapy, the challenges OVs face and solutions, and their combination with other biotherapeutic agents.

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Section: Various Types Of Ovsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Immunovirotherapy: The role of antibody based therapeutics combination with oncolytic viruses

Jafari

Kadkhodazadeh²,

Shapourabadi³

et al. 2022

Front. Immunol.

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Viral therapy for targeted drug delivery to cancers: Recent advances, clinical and regulatory perspectives

Dhuri,

Gharat,

Fernandes

et al. 2024

Journal of Drug Delivery Science and Technology

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A phase I oncolytic virus trial with vesicular stomatitis virus expressing human interferon beta and tyrosinase related protein 1 administered intratumorally and intravenously in uveal melanoma: safety, efficacy, and T cell responses

Smith,

Peng,

Pulido

et al. 2023

Front. Immunol.

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IntroductionMetastatic uveal melanoma (MUM) has a poor prognosis and treatment options are limited. These patients do not typically experience durable responses to immune checkpoint inhibitors (ICIs). Oncolytic viruses (OV) represent a novel approach to immunotherapy for patients with MUM.MethodsWe developed an OV with a Vesicular Stomatitis Virus (VSV) vector modified to express interferon-beta (IFN-β) and Tyrosinase Related Protein 1 (TYRP1) (VSV-IFNβ-TYRP1), and conducted a Phase 1 clinical trial with a 3 + 3 design in patients with MUM. VSV-IFNβ-TYRP1 was injected into a liver metastasis, then administered on the same day as a single intravenous (IV) infusion. The primary objective was safety. Efficacy was a secondary objective.Results12 patients with previously treated MUM were enrolled. Median follow up was 19.1 months. 4 dose levels (DLs) were evaluated. One patient at DL4 experienced dose limiting toxicities (DLTs), including decreased platelet count (grade 3), increased aspartate aminotransferase (AST), and cytokine release syndrome (CRS). 4 patients had stable disease (SD) and 8 patients had progressive disease (PD). Interferon gamma (IFNγ) ELIspot data showed that more patients developed a T cell response to virus encoded TYRP1 at higher DLs, and a subset of patients also had a response to other melanoma antigens, including gp100, suggesting epitope spreading. 3 of the patients who responded to additional melanoma antigens were next treated with ICIs, and 2 of these patients experienced durable responses.DiscussionOur study found that VSV-IFNβ -TYRP1 can be safely administered via intratumoral (IT) and IV routes in a previously treated population of patients with MUM. Although there were no clear objective radiographic responses to VSV-IFNβ-TYRP1, dose-dependent immunogenicity to TYRP1 and other melanoma antigens was seen.

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Perspectives for Combining Viral Oncolysis With Additional Immunotherapies for the Treatment of Melanoma

Cited by 3 publications

References 235 publications

Immunovirotherapy: The role of antibody based therapeutics combination with oncolytic viruses

Immunovirotherapy: The role of antibody based therapeutics combination with oncolytic viruses

Viral therapy for targeted drug delivery to cancers: Recent advances, clinical and regulatory perspectives

A phase I oncolytic virus trial with vesicular stomatitis virus expressing human interferon beta and tyrosinase related protein 1 administered intratumorally and intravenously in uveal melanoma: safety, efficacy, and T cell responses

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