Oncolytic Viruses—Interaction of Virus and Tumor Cells in the Battle to Eliminate Cancer

Howells, Anwen; Marelli, Giulia; Lemoine, Nicholas R.; Wang, Yaohe

doi:10.3389/fonc.2017.00195

Cited by 105 publications

(92 citation statements)

References 143 publications

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“…Proposition 5. There exists an optimal control pair (u * 1 , u * 2 ) with a corresponding solution (U * , I * , V * , C * ) to the model system (21) that minimizes J(u 1 , u 2 ) over Λ.…”

mentioning

confidence: 99%

Enhancement of chemotherapy using oncolytic virotherapy: Mathematical and optimal control analysis

Malinzi

Ouifki

Eladdadi

et al. 2018

Mathematical Biosciences &Amp; Engineering

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Oncolytic virotherapy has been emerging as a promising novel cancer treatment which may be further combined with the existing therapeutic modalities to enhance their effects. To investigate how virotherapy could enhance chemotherapy, we propose an ODE based mathematical model describing the interactions between tumour cells, the immune response, and a treatment combination with chemotherapy and oncolytic viruses. Stability analysis of the model with constant chemotherapy treatment rates shows that without any form of treatment, a tumour would grow to its maximum size. It also demonstrates that chemotherapy alone is capable of clearing tumour cells provided that the drug efficacy is greater than the intrinsic tumour growth rate. Furthermore, virotherapy alone may not be able to clear tumour cells from body tissue but would rather enhance chemotherapy if viruses with high viral potency are used. To assess the combined effect of virotherapy and chemotherapy we use the forward sensitivity index to perform a sensitivity analysis, with respect to chemotherapy key parameters, of the virus basic reproductive number and the tumour endemic equilibrium. The results from this sensitivity analysis indicate the existence of a critical dose of chemotherapy above which no further significant reduction in the tumour population can be observed. Numerical simulations show that a successful combinational therapy of the chemotherapeutic drugs and viruses depends mostly on the virus burst size, infection rate, and the amount of drugs supplied. Optimal control analysis was performed, by means of the Pontryagin's maximum principle, to further refine predictions of the model with constant treatment rates by accounting for the treatment costs and sides effects. Results from this analysis suggest that the optimal drug and virus combination correspond to half their maximum tolerated doses. This is in agreement with the results from stability and sensitivity analyses.2010 Mathematics Subject Classification. Primary: 49K15; Secondary: 92B05.

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“…Proposition 5. There exists an optimal control pair (u * 1 , u * 2 ) with a corresponding solution (U * , I * , V * , C * ) to the model system (21) that minimizes J(u 1 , u 2 ) over Λ.…”

mentioning

confidence: 99%

Enhancement of chemotherapy using oncolytic virotherapy: Mathematical and optimal control analysis

Malinzi

Ouifki

Eladdadi

et al. 2018

Mathematical Biosciences &Amp; Engineering

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“…Oncolytic viruses (OVs) have been used in viral oncotherapy for treating various types of cancers. They have a strong targeting efficacy with high specificity as shown in Figure . There are different types of OVs, including gamma retrovirus, lentivirus, adeno‐associated virus, and reovirus .…”

Section: Conventional Molecular Probes For Targeting Cancer Cellsmentioning

confidence: 99%

“…As a result, various types of RNA and DNA viruses can be engineered to target tumor cells selectively. Hence, OVs are proven to be safe and effective with minimal adverse effects in term of viral replications and lytic activity that support long lasting anticancer immune responses via memory T‐cells . The safety profile and selectivity of OVs can be significantly enhanced by leveraging the cellular pathways which are only upregulated in cancer cells.…”

Section: Conventional Molecular Probes For Targeting Cancer Cellsmentioning

confidence: 99%

“…The generation of safe and effective OVs via genetic engineering and the probing mechanism of OVs starting from infecting the tumor cells to viral replications and release to infect other neighboring tumor cells. Reproduced under the terms of the Creative Commons CC‐BY‐4.0 License . Copyright 2017, The Authors, published by Frontiers Media S.A.…”

Section: Conventional Molecular Probes For Targeting Cancer Cellsmentioning

confidence: 99%

“…There are diverse OVs killing mechanisms such as direct lysis, stimulation of immune response, autophagy, necrosis, expression of transgenes, direct cytotoxicity, and apoptosis . In addition, OVs are a good delivery vector to carry either in vivo or in vitro therapeutic genes via genetic modification for cancer therapies . A desired OV vector is able to transfer the desired therapeutic gene within its viral genome to the target cell for gene expression, specifically using the targeted cancerous membrane receptor protein.…”

Section: Conventional Molecular Probes For Targeting Cancer Cellsmentioning

confidence: 99%

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Advancing Aptamers as Molecular Probes for Cancer Theranostic Applications—The Role of Molecular Dynamics Simulation

Jeevanandam

Tan

Danquah

et al. 2020

Biotechnology Journal

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Theranostics cover emerging technologies for cell biomarking for disease diagnosis and targeted introduction of drug ingredients to specific malignant sites. Theranostics development has become a significant biomedical research endeavor for effective diagnosis and treatment of diseases, especially cancer. An efficient biomarking and targeted delivery strategy for theranostic applications requires effective molecular coupling of binding ligands with high affinities to specific receptors on the cancer cell surface. Bioaffinity offers a unique mechanism to bind specific target and receptor molecules from a range of non‐targets. The binding efficacy depends on the specificity of the affinity ligand toward the target molecule even at low concentrations. Aptamers are fragments of genetic materials, peptides, or oligonucleotides which possess enhanced specificity in targeting desired cell surface receptor molecules. Aptamer–target binding results from several inter‐molecular interactions including hydrogen bond formation, aromatic stacking of flat moieties, hydrophobic interaction, electrostatic, and van der Waals interactions. Advancements in Systematic Evolution of Ligands by Exponential Enrichment (SELEX) assay has created the opportunity to artificially generate aptamers that specifically bind to desired cancer and tumor surface receptors with high affinities. This article discusses the potential application of molecular dynamics (MD) simulation to advance aptamer‐mediated receptor targeting in targeted cancer therapy. MD simulation offers real‐time analysis of the molecular drivers of the aptamer‐receptor binding and generate optimal receptor binding conditions for theranostic applications. The article also provides an overview of different cancer types with focus on receptor biomarking and targeted treatment approaches, conventional molecular probes, and aptamers that have been explored for cancer cells targeting.

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The viral approach to breast cancer immunotherapy

Arab

Behravan²,

Razazn

et al. 2018

Journal Cellular Physiology

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Despite years of intensive research, breast cancer remains the leading cause of death in women worldwide. New technologies including oncolytic virus therapies, virus, and phage display are among the most powerful and advanced methods that have emerged in recent years with potential applications in cancer prevention and treatment. Oncolytic virus therapy is an interesting strategy for cancer treatment. Presently, a number of viruses from different virus families are under laboratory and clinical investigation as oncolytic therapeutics. Oncolytic viruses (OVs) have been shown to be able to induce and initiate a systemic antitumor immune response. The possibility of application of a multimodal therapy using a combination of the OV therapy with immune checkpoint inhibitors and cancer antigen vaccination holds a great promise in the future of cancer immunotherapy. Display of immunologic peptides on bacterial viruses (bacteriophages) is also increasingly being considered as a new and strong cancer vaccine delivery strategy. In phage display immunotherapy, a peptide or protein antigen is presented by genetic fusions to the phage coat proteins, and the phage construct formulation acts as a protective or preventive vaccine against cancer. In our laboratory, we have recently tested a few peptides (E75, AE37, and GP2) derived from HER2/neu proto-oncogene as vaccine delivery modalities for the treatment of TUBO breast cancer xenograft tumors of BALB/c mice. Here, in this paper, we discuss the latest advancements in the applications of OVs and bacterial viruses display systems as new and advanced modalities in cancer immune therapeutics.

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Oncolytic Viruses—Interaction of Virus and Tumor Cells in the Battle to Eliminate Cancer

Cited by 105 publications

References 143 publications

Enhancement of chemotherapy using oncolytic virotherapy: Mathematical and optimal control analysis

Enhancement of chemotherapy using oncolytic virotherapy: Mathematical and optimal control analysis

Advancing Aptamers as Molecular Probes for Cancer Theranostic Applications—The Role of Molecular Dynamics Simulation

The viral approach to breast cancer immunotherapy

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