Viruses – seeking and destroying the tumor program

O’Shea, Clodagh C.

doi:10.1038/sj.onc.1209047

Cited by 58 publications

(57 citation statements)

References 183 publications

(128 reference statements)

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“…Unlike more conventional forms of gene-based cancer therapy, these conditionally replicating viruses kill tumor cells directly through selective replication/cytolysis and consequent spread to surrounding tumor tissues (2). These properties represent a major advantage over the inherent inefficiency of therapeutic gene delivery and the resultant diminution of tumor cell killing activity.…”

mentioning

confidence: 99%

Virotherapy with a Type 2 Herpes Simplex Virus–Derived Oncolytic Virus Induces Potent Antitumor Immunity against Neuroblastoma

Dutuor

Tao

et al. 2007

Clinical Cancer Research

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Purpose: We recently constructed an oncolytic virus from type 2 herpes simplex virus that selectively targets and kills tumor cells with an activated Ras signaling pathway. Designated FusOn-H2, this virus has shown several discrete killing mechanisms. Here, we evaluated the antitumor immune responses after FusOn-H2^mediated virotherapy in a syngeneic murine neuroblastoma model. Experimental Design: We directly injected FusOn-H2 into established tumors and then measured its antitumor effect and the accompanying tumor-specific immune responses. Several oncolytic HSVs constructed from HSV-1were included in the same experiments for comparisons. Results: Our data show that tumor destruction by FusOn-H2 in vivo induces potent antitumor immune responses in this syngeneic neuroblastoma model. The elicited cellular immunity not only eradicated neuroblastoma cells in vitro but also inhibited the growth of tumors at sites distant from the virus injection site. Moreover, adoptive transfer of splenocytes from mice receiving virotherapy to naI« ve mice resulted in a measurable antitumor effect. Conclusion: We conclude that the ability of FusOn-H2 to induce tumor-specific cellular immunity expands the oncolytic repertoire of this virus and increases the likelihood that its use in patients would produce significant therapeutic benefits.

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mentioning

confidence: 99%

Virotherapy with a Type 2 Herpes Simplex Virus–Derived Oncolytic Virus Induces Potent Antitumor Immunity against Neuroblastoma

Dutuor

Tao

et al. 2007

Clinical Cancer Research

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“…Tumor destruction by an oncolytic virus can release a wide range of tumor specific antigens that will be taken up by infiltrating antigen-presenting cells for cross-presentation to T cells for priming of antigen-specific immune response (O'Shea, 2005). Moreover, different stimuli can promote an immunogenic cell death of tumor cells.…”

Section: Oncolytic Poliovirus For Treatment Of Neuroblastoma: Preclinmentioning

confidence: 99%

Oncolytic Poliovirus Therapy in a Mouse Model of Neuroblastoma: Preclinical Data Analysis and Future Studies

Toyoda¹,

Wimmer²,

Cello³

2012

Neuroblastoma - Present and Future

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“…Tumor destruction by an oncolytic virus can release a wide range of tumor-specific antigens that will be taken up by infiltrating antigen-presenting cells for cross-presentation to T cells for priming of antigenspecific immune response (25). Based on this premise, we reasoned that immunization with an in vitro PV-infected neuroblastoma cell lysate should be able to prime an effective immune response against tumor cells and subsequently hinder neuroblastoma growth (see Materials and methods and Fig.…”

Section: Induction Of Antitumor Immune Response By Lysates Of Pvinfecmentioning

confidence: 99%

Oncolytic poliovirus therapy and immunization with poliovirus-infected cell lysate induces potent antitumor immunity against neuroblastoma in vivo

Toyoda

Wimmer²,

Cello³

2010

Int J Oncol

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Abstract. In a previous study, we demonstrated that neuroblastoma subcutaneously implanted in immuno-competent mice is eliminated by intratumoral administration of neuroattenuated poliovirus (PV). Our results also suggested that the in vivo destruction of neuroblastoma cells by virotherapy lead to a robust antitumor immune response. In this work, splenocytes harvested from neuroblastoma-bearing animals treated with neuroattenuated PV exhibited significantly higher lytic activity against tumor target cells than did those from splenocytes derived from control mice. In vitro T-cell depletion experiments indicated that CD8 + T cells were essential for the cytotoxic antitumor activity of splenocytes. Moreover, adoptive transfer of splenocytes obtained from mice cured of neuroblastoma by PV virotherapy markedly delayed the tumor growth of previously established neuroblastomas in recipient naïve mice. These results confirmed that treatment with a neuroattenuated oncolytic PV strain induces antitumor immunity against neuroblastoma that is mainly mediated by cytotoxic CD8 + T cells. Immunocompetent mice, on the other hand, were immunized with PV-infected neuroblastoma cell lysate prior intravenous challenge with neuroblastoma cells. As a control, mice were vaccinated with either non-infected neuroblastoma cell lysate alone or mixed with PV, or with PBS prior tumor cell injection. Results showed that survival is significantly prolonged only in mice immunized with PV-infected tumor lysate. This finding clearly suggested that in vitro poliovirus infection of neuroblastoma cells turns these cells into a potent tumor immunogen. Further studies in oncolytic treatment of neuroblastoma using attenuated PV alone or in combination with immunotherapy with PV oncolysate should improve the probability for successful translation in the clinic.

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Viruses – seeking and destroying the tumor program

Cited by 58 publications

References 183 publications

Virotherapy with a Type 2 Herpes Simplex Virus–Derived Oncolytic Virus Induces Potent Antitumor Immunity against Neuroblastoma

Virotherapy with a Type 2 Herpes Simplex Virus–Derived Oncolytic Virus Induces Potent Antitumor Immunity against Neuroblastoma

Oncolytic Poliovirus Therapy in a Mouse Model of Neuroblastoma: Preclinical Data Analysis and Future Studies

Oncolytic poliovirus therapy and immunization with poliovirus-infected cell lysate induces potent antitumor immunity against neuroblastoma in vivo

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