Gene Therapy of Melanoma Using Inactivated Sendai Virus Envelope Vector (HVJ-E) with Intrinsic Anti-Tumor Activities

Kaneda, Yasufumi; Kiyohara, Eiji; Nakajima, Takeshi; Itai, Toshimitsu

doi:10.5772/17492

Cited by 2 publications

(3 citation statements)

References 28 publications

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“…In this study, a dose‐dependent increase in RIG‐I expression as well as apoptosis and cell death was observed in mouse‐derived B16F10 melanoma cells following HVJ‐E treatment. In contrast to human cancer cells, in which HVJ‐E induced production of a large amount of type I IFN, only a very small amount of IFN‐β was produced in murine melanoma cells after HVJ‐E treatment, consistent with previous reports . The underlying mechanism of type I IFN production in human and murine cancer cells in response to HVJ‐E remains unknown.…”

Section: Discussionsupporting

confidence: 89%

“…In contrast to human cancer cells, in which HVJ-E induced production of a large amount of type I IFN, 12 only a very small amount of IFN-b was produced in murine melanoma cells after HVJ-E treatment, consistent with previous reports. [29][30][31] The underlying mechanism of type I IFN pro-duction in human and murine cancer cells in response to HVJ-E remains unknown.…”

Section: Discussionmentioning

confidence: 99%

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IPS‐1 plays a dual function to directly induce apoptosis in murine melanoma cells by inactivated Sendai virus

Zhang

Yuan

et al. 2013

Intl Journal of Cancer

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Inactivated Sendai virus (HVJ-E) directly kills cancer cells by inducing apoptosis through a mechanism mediated by Janus kinases=signal transducers and activators of transcription (JAK=STAT) signaling pathways. However, whether other signaling pathways are involved remain largely unknown. This study aimed to investigate the mechanism underlying HVJ-E-induced apoptosis in murine B16F10 melanoma cells. We found that HVJ-E induced B16F10 cell apoptosis via the caspase pathway, particularly caspase-9, which mediates the intrinsic apoptotic pathway. Mitogen-activated protein kinase (MAPK) pathway activation also contributed to HVJ-E-induced apoptosis. Whereas caspase pathway involvement depended on both IFN-b promoter stimulator-1 (IPS-1) and type I interferon (IFN), MAPK pathway activation was independent of type I IFN but involved IPS-1. In addition, intratumoral HVJ-E treatment displayed a direct oncolytic effect in an in vivo BALB=c nude mouse melanoma model. Collectively, our data provides new insights into the mechanism underlying HVJ-E-induced apoptosis in tumor cells.

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Section: Discussionsupporting

confidence: 89%

Section: Discussionmentioning

confidence: 99%

IPS‐1 plays a dual function to directly induce apoptosis in murine melanoma cells by inactivated Sendai virus

Zhang

Yuan

et al. 2013

Intl Journal of Cancer

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“…Indeed, an increase in therapeutic efficacy has been reported for virotherapies combined with photodynamic therapy [98,99], radiotherapy [100], chemotherapy [101,102], or gene therapy [103]. Kiyohara and Kaneda reported that combination of the non-replicating virus (HVJ-E) and gene therapy (IL-12) increased efficacy in a murine model of melanoma [104]. Furthermore, it was reported that a combination of non-replicating virus (HVJ-E) and chemotherapy [bleomycin or cis-diamminedichloroplatinum (CDDP)] increased efficacy in murine models of colon and bladder cancers [78,105].…”

Section: Future Perspectivesmentioning

confidence: 99%

A Novel Therapy for Melanoma and Prostate Cancer Using a Non-Replicating Sendai Virus Particle (HVJ-E)

Nakajima¹,

Itai²,

Wada³

et al. 2013

Novel Gene Therapy Approaches

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An alternative option to avoid such a risk is to use a non-replicating oncolytic virus [44]. We found that a non-replicating oncolytic virus (HVJ-E: hemagglutinating virus of Japanenvelope) is able to induce cancer cell-specific apoptosis and immunity [45]. The induction of apoptosis and activation of dendritic cells in vitro, and anti-tumor activity in vivo are similar to the wild-type hemagglutinating virus of Japan (also known as Sendai virus, HVJ) [45]. The hemagglutinating virus of Japan was discovered in Sendai, Japan, in the 1950s [46]. It is a paramyxovirus with a minus-strand RNA genome. The virus has fusogenic activity [47, 48], and is used to prepare hybridoma cells for the production of monoclonal antibodies, and heterokaryons for chromosome analysis [49-51]. The hemagglutinating virus of Japan-envelope is an inactivated HVJ particle [52]. It is manufactured by a process similar to that used for whole virus particle vaccines. Good manufacturing practice (GMP)-regulated processes have been established in their production for use in preclinical and clinical studies [53]. We conducted dose-setting efficacy studies for HVJ-E in a murine cancer model in which dosedependent anti-cancer activity was observed. We also conducted safety studies following good laboratory practices (GLP), including pharmacological safety studies and toxicokinetic (TK) studies in rats and monkeys, as part of an investigational new drug (IND) application. Osaka University Hospital is currently conducting two investigational clinical studies with HVJ-E for the treatment of advanced melanoma and castration-resistant prostate cancer (CRPC) [54-56]. These clinical trials are the first human studies for HVJ-E and will reveal the safety and efficacy of the non-replicating virus (HVJ-E). Virotherapy with a non-replicating oncolytic virus is a new approach that is anticipated to provide a new strategy for cancer therapy. 2. A new strategy for cancer therapy Most cancers are still incurable and new approaches are required to improve the efficacy of cancer treatments. However, conventional cancer therapies are problematic. Chemotherapy with anti-cancer agents is useful in achieving tumor regression. However, the immune system, which is important in the removal of residual cancer cells, is also suppressed by these agents (Figure 1). Therefore, surviving cancer cells and cancer stem cells (CSC) eventually acquire drug resistance, resulting in tumor relapse (Figure 1) [57]. Thus, chemotherapy with cytotoxic drugs does not generally result in the necessary eradication of cancer cells required for long-term survival. Immune therapies for cancer offer a new approach to cancer treatment, and several products, including sipuleucel-T, are currently approved in advanced countries [58, 59]. The aim of these therapies is the removal of cancers by the immune system. Numerous cancer immune therapies are currently under evaluation in clinical studies. However, these agents are not potent because of lack of cytotoxic effect on cancer cells (Figure 1).

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Gene Therapy of Melanoma Using Inactivated Sendai Virus Envelope Vector (HVJ-E) with Intrinsic Anti-Tumor Activities

Cited by 2 publications

References 28 publications

IPS‐1 plays a dual function to directly induce apoptosis in murine melanoma cells by inactivated Sendai virus

IPS‐1 plays a dual function to directly induce apoptosis in murine melanoma cells by inactivated Sendai virus

A Novel Therapy for Melanoma and Prostate Cancer Using a Non-Replicating Sendai Virus Particle (HVJ-E)

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