Theranostic Tripartite Cancer Terminator Virus for Cancer Therapy and Imaging

Bhoopathi, Praveen; Pradhan, Anjan K.; Maji, Santanu; Das, Swadesh K.; Emdad, Luni; Fisher, Paul B.

doi:10.3390/cancers13040857

Cited by 5 publications

(2 citation statements)

References 76 publications

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“…In an interesting study, Bhoopathi et al introduced a novel tripartite CTV "theranostic" adenovirus (TCTV) that targets virus replication, cytokine production, and imaging capabilities uniquely in cancer cells. This TCTV permits targeted treatment of tumors while monitoring tumor regression, with the potential to simultaneously detect metastasis due to the cancer-selective activity of reporter gene expression (102).…”

Section: Discussionmentioning

confidence: 99%

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

et al. 2021

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The global rate of cancer has increased in recent years, and cancer is still a threat to human health. Recent developments in cancer treatment have yielded the understanding that viruses have a high potential in cancer treatment. Using oncolytic viruses (OVs) is a promising approach in the treatment of malignant tumors. OVs can achieve their targeted treatment effects through selective cell death and induction of specific antitumor immunity. Targeting tumors and the mechanism for killing cancer cells are among the critical roles of OVs. Therefore, evaluating OVs and understanding their precise mechanisms of action can be beneficial in cancer therapy. This review study aimed to evaluate OVs and the mechanisms of their effects on cancer cells.

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Section: Discussionmentioning

confidence: 99%

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

et al. 2021

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“…This virus, also called a cancer terminator virus (CTV), induces cancer-specific replication and a second CMV promoter in the virus promotes MDA-7/IL-24 expression uniquely in cancer cells as a consequence of virus replication [ 83 , 84 , 96 ]. The robust and superior cancer selective activity of the CTV (developed both in serotype 5 ad 5/3 Ads) was validated in diverse cancers including prostate, glioma, melanoma, breast, pancreatic and neuroblastoma both in vitro and in vivo using established cancer cell lines, patient-derived cancer cells, human tumor xenografts in nude mice, murine tumor xenografts in immune competent mice and genetically engineered transgenic mouse models of several cancers [ 8 , 9 , 10 , 83 , 84 , 90 , 96 , 99 , 100 , 101 ]. Another CRCA (ZD55-IL-24) was created to deliver mda-7/IL-24 using the ZD55 vector, in which the adenoviral E1B 55-kDa gene was deleted to control replication in cancer cells with p53 dysfunction.…”

Section: Mda-7/il-24 As a Single Therapeuticmentioning

confidence: 99%

Insights into the Mechanisms of Action of MDA-7/IL-24: A Ubiquitous Cancer-Suppressing Protein

Modi

Roy

Pradhan

et al. 2021

IJMS

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Melanoma differentiation associated gene-7/interleukin-24 (MDA-7/IL-24), a secreted protein of the IL-10 family, was first identified more than two decades ago as a novel gene differentially expressed in terminally differentiating human metastatic melanoma cells. MDA-7/IL-24 functions as a potent tumor suppressor exerting a diverse array of functions including the inhibition of tumor growth, invasion, angiogenesis, and metastasis, and induction of potent “bystander” antitumor activity and synergy with conventional cancer therapeutics. MDA-7/IL-24 induces cancer-specific cell death through apoptosis or toxic autophagy, which was initially established in vitro and in preclinical animal models in vivo and later in a Phase I clinical trial in patients with advanced cancers. This review summarizes the history and our current understanding of the molecular/biological mechanisms of MDA-7/IL-24 action rendering it a potent cancer suppressor.

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Noninvasive therapy of brain cancer using a unique systemic delivery methodology with a cancer terminator virus

Bhoopathi,

Mannangatti,

Pradhan

et al. 2024

Journal Cellular Physiology

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Primary, glioblastoma, and secondary brain tumors, from metastases outside the brain, are among the most aggressive and therapeutically resistant cancers. A physiological barrier protecting the brain, the blood–brain barrier (BBB), functions as a deterrent to effective therapies. To enhance cancer therapy, we developed a cancer terminator virus (CTV), a unique tropism‐modified adenovirus consisting of serotype 3 fiber knob on an otherwise Ad5 capsid that replicates in a cancer‐selective manner and simultaneously produces a potent therapeutic cytokine, melanoma differentiation‐associated gene‐7/interleukin‐24 (MDA‐7/IL‐24). A limitation of the CTV and most other viruses, including adenoviruses, is an inability to deliver systemically to treat brain tumors because of the BBB, nonspecific virus trapping, and immune clearance. These obstacles to effective viral therapy of brain cancer have now been overcome using focused ultrasound with a dual microbubble treatment, the focused ultrasound‐double microbubble (FUS‐DMB) approach. Proof‐of‐principle is now provided indicating that the BBB can be safely and transiently opened, and the CTV can then be administered in a second set of complement‐treated microbubbles and released in the brain using focused ultrasound. Moreover, the FUS‐DMB can be used to deliver the CTV multiple times in animals with glioblastoma growing in their brain thereby resulting in a further enhancement in survival. This strategy permits efficient therapy of primary and secondary brain tumors enhancing animal survival without promoting harmful toxic or behavioral side effects. Additionally, when combined with a standard of care therapy, Temozolomide, a further increase in survival is achieved. The FUS‐DMB approach with the CTV highlights a noninvasive strategy to treat brain cancers without surgery. This innovative delivery scheme combined with the therapeutic efficacy of the CTV provides a novel potential translational therapeutic approach for brain cancers.

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Theranostic Tripartite Cancer Terminator Virus for Cancer Therapy and Imaging

Cited by 5 publications

References 76 publications

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

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

Insights into the Mechanisms of Action of MDA-7/IL-24: A Ubiquitous Cancer-Suppressing Protein

Noninvasive therapy of brain cancer using a unique systemic delivery methodology with a cancer terminator virus

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