Oncolytic Viruses and Cancer, Do You Know the Main Mechanism?

Kooti, Wesam; Ghaleh, Hadi Esmaeili Gouvarchin; Farzanehpour, Mahdieh; Dorostkar, Ruhollah; Kondori, Bahman Jalali; Bolandian, Masoumeh

doi:10.3389/fonc.2021.761015

Cited by 19 publications

(10 citation statements)

References 98 publications

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“…To test whether selinexor can enhance MYXV replication in the 3D culture of human cancer cells, we established a 3D cell culture using type I collagen. 7 FFU on right tumor only). Animals received total 4 treatments within the first two weeks and tumor burden was measured 2-3 times every week.…”

Section: Selinexor Enhances Myxv Replication In 3d Human Cancer Cell ...mentioning

confidence: 99%

“…Selinexor alone (oral), vMyx-Fluc (wild-type MYXV expressing Firefly Luc and TdTomato) alone (IT, 1x10 7 FFU on left tumor only), PBS (oral and IT) or Selinexor (oral) + vMyx-Fluc (IT, 1x10 7 FFU on left tumor only) simultaneously. After 48 h post-first treatment, mice were imaged using the IVIS system for luciferase expression.…”

Section: Selinexor Enhances Myxv Replication In 3d Human Cancer Cell ...mentioning

confidence: 99%

“…An ideal replication-competent OV is expected to selectively infect, replicate, and generate progeny virions in the infected cancer cells, which subsequently will infect the neighboring cancer cells in the tumor bed (4,5). This successful replication of OVs is thought to mediate antitumoral activity in multiple ways, such as the direct killing of infected cancer cells, exposing and presenting novel tumor specific neoantigens, activation of systemic antitumor and antiviral immunity, and recruitment of activated immune cells to the tumor microenvironment (TME) (6,7). In addition to its own multi-mechanistic antitumor activity, OVs can be combined with most of the currently approved cancer therapeutics, such as chemotherapies, immune checkpoint inhibitors and cell therapies, for additional therapeutic benefits (8)(9)(10)(11).…”

Section: Introductionmentioning

confidence: 99%

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A novel anti-cancer therapy with nuclear export inhibitor Selinexor in combination with oncolytic myxoma virus

Rahman¹,

Oosterom²,

Enow³

et al. 2022

Preprint

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Oncolytic viruses exploited for cancer therapy are developed to selectively infect, replicate, and kill cancer cells to stop tumor growth. However, in some cancer cells, oncolytic viruses are often limited in completing their full replication cycle, making progeny virions, and/or spread in the tumor bed due to the heterogeneous cell types within the tumor bed. Here we report that nuclear export pathway regulates oncolytic myxoma virus (MYXV) infection and cytoplasmic viral replication in a subclass of human cancer cell types where virus replication is restricted. Inhibition of CRM1/XPO-1 nuclear export pathway with nuclear export inhibitors can overcome this restriction by trapping restriction factors in the nucleus and allow significantly enhanced virus replication and killing of human cancer cells. Furthermore, knockdown of CRM1/XPO-1 significantly enhanced MYXV replication in restrictive human cancer cells and reduced the formation of anti-viral granules associated with RNA helicase DHX9. Both in vitro and in vivo, we demonstrate that the approved CRM1 inhibitor drug Selinexor enhances the replication of MYXV and cell killing of diverse human cancer cells. In the xenograft tumor model in NSG mice, combination therapy with Selinexor plus MYXV significantly reduced tumor burden and enhanced the survival of animals. Additionally, we performed global scale proteomic analysis of nuclear and cytosolic proteins in human cancer cells to identify the host and viral proteins that are upregulated or downregulated by different treatments. These results for the first time indicate that Selinexor in combination with oncolytic MYXV can be used as potential new anti-cancer therapy.

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Section: Selinexor Enhances Myxv Replication In 3d Human Cancer Cell ...mentioning

confidence: 99%

Section: Selinexor Enhances Myxv Replication In 3d Human Cancer Cell ...mentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

A novel anti-cancer therapy with nuclear export inhibitor Selinexor in combination with oncolytic myxoma virus

Rahman¹,

Oosterom²,

Enow³

et al. 2022

Preprint

View full text Add to dashboard Cite

show abstract

“…Herpes simplex virus, adenovirus, and Coxsackievirus have different clinical applications in cancer treatment [2] . OVs can achieve their targeted treatment effects through selective cell death and induction of specific antitumor immunity [15] .…”

Section: Viruses and Cancermentioning

confidence: 99%

SARS-CoV-2 and cancer: the intriguing and informative cross-talk

Goubran

Stakiw

Seghatchian

et al. 2022

Transfusion and Apheresis Science

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“…These therapies have fewer secondary effects and present a clear advantage in veterinary oncology, given that they are more tolerable by the patient than conventional therapies, allowing the animals to maintain their quality of life [ 17 ]. Although there are many varieties of immunotherapy, the use of oncolytic viruses (OVs) is an innovative approach that has become an interesting field of research, with several promising results as an oncological treatment [ 21 , 22 , 23 , 24 ].…”

Section: Introductionmentioning

confidence: 99%

Safety and Efficacy of an Oncolytic Adenovirus as an Immunotherapy for Canine Cancer Patients

Martín-Carrasco

Delgado-Bonet

Tomeo-Martín

et al. 2022

Veterinary Sciences

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The use of oncolytic viruses is an innovative approach to lyse tumor cells and induce antitumor immune responses. Eight dogs diagnosed with carcinoma/adenocarcinoma were intratumorally treated with ICOCAV15, an oncolytic canine adenovirus (CAV). To evaluate the treatment’s safety, a blood count, biochemistry, and coagulation test were performed before treatment and during follow-up. Immune populations were analyzed by flow cytometry. Anti-adenovirus antibodies were also determined. The immune infiltration, vascularization, and viral presence in the tumor were determined by CD3, CD4, CD20, CD31 and CAV by immunohistochemistry. All the dogs maintained a good quality of life during follow-up, and some had increased median survival time when compared with dogs treated with chemotherapy. No treatment-related adverse effects were detected. The Response Evaluation Criteria In Solid Tumors criteria were also assessed: two patients showed a partial response and the rest showed stable disease at various times during the study. ICOCAV15 was detected inside the tumor during follow-up, and antiviral antibodies were detected in all patients. Furthermore, the tumor-infiltrating immune cells increased after viral administration. Therefore, we suggest that intratumorally administered ICOCAV15 could represent as a new tool for the treatment of canine carcinoma because it is safe, well-tolerated by dogs, and shows promising results.

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Oncolytic Viruses and Cancer, Do You Know the Main Mechanism?

Cited by 19 publications

References 98 publications

A novel anti-cancer therapy with nuclear export inhibitor Selinexor in combination with oncolytic myxoma virus

A novel anti-cancer therapy with nuclear export inhibitor Selinexor in combination with oncolytic myxoma virus

SARS-CoV-2 and cancer: the intriguing and informative cross-talk

Safety and Efficacy of an Oncolytic Adenovirus as an Immunotherapy for Canine Cancer Patients

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