Dependency of EGFR activation in vanadium-based sensitization to oncolytic virotherapy

Wong, Boaz; Bergeron, Anabel; Alluqmani, Nouf; Maznyi, Glib; Chen, Andrew; Arulanandam, Rozanne; Diallo, Jean-Simon

doi:10.1016/j.omto.2022.04.004

Cited by 4 publications

(4 citation statements)

References 78 publications

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“…The elevated levels of IL-6 observed peaking at 5 days post treatment in this study are therefore consistent with an increase in tumor-antigen-specific T-cell response ( Figure 2 ). This observation is also consistent with previous in vitro studies, implicating EGFR pathway activation as a molecular mechanism of vanadium compounds, leading to simultaneous downregulation of STAT2 and hyperactivation of both STAT1 and NF-kB ( 19 ). On the other hand, IL-6 is also suspected to play a role in tumour development ( 35 ) and some groups have found a correlation between high circulating levels of IL-6 and poor prognosis in cancer patients ( 36 ).…”

Section: Discussionsupporting

confidence: 93%

“…CXCL9, CXCL10), a phenomenon observed in both human 786-0 and mouse CT26WT cell lines ( 9 , 10 ). Recent studies have further shown that the observed effect on STAT1/STAT2 ratios involves vanadate/VSVΔ51 induced hyperactivation of the the epidermal growth factor receptor (EGFR) receptor and downstream pathways including NF-kB (Nuclear Factor Kappa B) ( 19 ). Supporting this mechanism, Gefitinib, an EGFR antagonist, abrogated the enhancing effect of vanadium in vivo in a syngeneic CT26WT model ( 19 ).…”

Section: Introductionmentioning

confidence: 99%

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Vanadyl sulfate-enhanced oncolytic virus immunotherapy mediates the antitumor immune response by upregulating the secretion of pro-inflammatory cytokines and chemokines

Alluqmani

Jirovec²,

Taha³

et al. 2022

Front. Immunol.

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Oncolytic viruses (OVs) are promising anticancer treatments that specifically replicate in and kill cancer cells and have profound immunostimulatory effects. We previously reported the potential of vanadium-based compounds such as vanadyl sulfate (VS) as immunostimulatory enhancers of OV immunotherapy. These compounds, in conjunction with RNA-based OVs such as oncolytic vesicular stomatitis virus (VSVΔ51), improve viral spread and oncolysis, leading to long-term antitumor immunity and prolonged survival in resistant tumor models. This effect is associated with a virus-induced antiviral type I IFN response shifting towards a type II IFN response in the presence of vanadium. Here, we investigated the systemic impact of VS+VSVΔ51 combination therapy to understand the immunological mechanism of action leading to improved antitumor responses. VS+VSVΔ51 combination therapy significantly increased the levels of IFN-γ and IL-6, and improved tumor antigen-specific T-cell responses. Supported by immunological profiling and as a proof of concept for the design of more effective therapeutic regimens, we found that local delivery of IL-12 using VSVΔ51 in combination with VS further improved therapeutic outcomes in a syngeneic CT26WT colon cancer model.

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Section: Discussionsupporting

confidence: 93%

Section: Introductionmentioning

confidence: 99%

Vanadyl sulfate-enhanced oncolytic virus immunotherapy mediates the antitumor immune response by upregulating the secretion of pro-inflammatory cytokines and chemokines

Alluqmani

Jirovec²,

Taha³

et al. 2022

Front. Immunol.

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“…It has been demonstrated that sodium orthovanadate (vanadate) through the epidermal growth factor receptor (EGFR) pathway can overcome tumor resistance to these viruses and improve the antitumor effects of RNA‐based oncolytic viruses in a synergistic fashion. [ 62 ]…”

Section: Boundaries Of Virotherapymentioning

confidence: 99%

Combining of Oncolytic Virotherapy and Other Immunotherapeutic Approaches in Cancer: A Powerful Functionalization Tactic

2022

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to direct lysis of these cells. [4] In addition, oncolytic viruses can stimulate immune responses. The most studied oncolytic viruses are Newcastle disease viruses, herpes viruses, coxsackievirus, measles viruses, adenoviruses, polioviruses, poxviruses, and reoviruses. [5,6] Therefore, oncolytic viruses can be a moral treatment option in cancer therapy. The unique feature of oncolytic viruses is that they act selectively and remove tumor cells without damaging non-cancerous cells. [7] Initially, oncolytic virotherapy was studied as monotherapy with unsatisfactory therapeutic effectiveness. Several mechanisms, including the immunosuppressive tumor microenvironment (TME), the off-target sequestration and replication, the existence of neutralizing antibodies, and the balance between viral replication and induced immune response, contribute to oncolytic virotherapy monotherapy resistance. [8] Therefore, researchers have used various combination therapies to overcome these barriers using oncolytic viruses and immunotherapy.Cancer immunotherapy, including methods such as adoptive T cell therapy, immune checkpoint blockade, and monoclonal or bispecific antibodies, has recently succeeded in treating cancer and other immune-related diseases such as autoimmunity. [9][10][11] Oncolytic viruses have found a good place in the treatment of cancer. Administering oncolytic viruses directly or by applying genetic changes can be effective in cancer treatment through the lysis of tumor cells and, in some cases, by inducing immune system responses. Moreover, oncolytic viruses induce antitumor immune responses via releasing tumor antigens in the tumor microenvironment (TME) and affect tumor cell growth and metabolism. Despite the success of virotherapy in cancer therapies, there are several challenges and limitations, such as immunosuppressive TME, lack of effective penetration into tumor tissue, low efficiency in hypoxia, antiviral immune responses, and off-targeting. Evidence suggests that oncolytic viruses combined with cancer immunotherapy-based methods such as immune checkpoint inhibitors and adoptive cell therapies can effectively overcome these challenges. This review summarizes the latest data on the use of oncolytic viruses for the treatment of cancer and the challenges of this method. Additionally, the effectiveness of mono, dual, and triple therapies using oncolytic viruses and other anticancer agents has been discussed based on the latest findings.

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“…OVs can selectively reproduce in cancer cells and propagate throughout a tumor without affecting the healthy tissues ( 39 , 40 ). Despite some viruses’ natural tropism for tumors, the wide range of tumor forms and histologic origins makes it challenging to link OVs to a specific malignancy ( 41 , 42 ).…”

Section: Intro To Virotherapy: From Concept To Bedsidementioning

confidence: 99%

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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Dependency of EGFR activation in vanadium-based sensitization to oncolytic virotherapy

Cited by 4 publications

References 78 publications

Vanadyl sulfate-enhanced oncolytic virus immunotherapy mediates the antitumor immune response by upregulating the secretion of pro-inflammatory cytokines and chemokines

Vanadyl sulfate-enhanced oncolytic virus immunotherapy mediates the antitumor immune response by upregulating the secretion of pro-inflammatory cytokines and chemokines

Combining of Oncolytic Virotherapy and Other Immunotherapeutic Approaches in Cancer: A Powerful Functionalization Tactic

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

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