Potent Oncolytic activity of human enteroviruses against human prostate cancer

Berry, Linda J.; Au, Gough G.; Barry, Richard D.; Shafren, Darren R.

doi:10.1002/pros.20741

Cited by 40 publications

(29 citation statements)

References 49 publications

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“…9,10,16–18 Another factor of probable relevance was the high dose of virus administered. Dose-response relationships for antitumor efficacy and virus delivery have been well documented in previous virotherapy studies, 7,15,19,20 and a dose-threshold effect can be mathematically predicted. 20 Also, measles virus transcripts were still detectable in the circulating cells of patient 1 at 6 weeks after virus infusion, by which time there had been a substantial boost to her antimeasles antibody titer, suggesting the possibility of continuing ongoing oncolytic activity even at that late time.…”

Section: Discussionmentioning

confidence: 88%

Remission of Disseminated Cancer After Systemic Oncolytic Virotherapy

Russell

Federspiel

Peng

et al. 2014

Mayo Clinic Proceedings

240

261

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MV-NIS is an engineered measles virus that is selectively destructive to myeloma plasma cells and can be monitored by noninvasive radioiodine imaging of NIS gene expression. Two measles-seronegative patients with relapsing drug-refractory myeloma and multiple glucose-avid plasmacytomas were treated by intravenous infusion of 1011 TCID50 (50% tissue culture infectious dose) infectious units of MV-NIS. Both patients responded to therapy with M protein reduction and resolution of bone marrow plasmacytosis. Further, one patient experienced durable complete remission at all disease sites. Tumor targeting was clearly documented by NIS-mediated radioiodine uptake in virus-infected plasmacytomas. Toxicities resolved within the first week after therapy. Oncolytic viruses offer a promising new modality for the targeted infection and destruction of disseminated cancer.

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Section: Discussionmentioning

confidence: 88%

Remission of Disseminated Cancer After Systemic Oncolytic Virotherapy

Russell

Federspiel

Peng

et al. 2014

Mayo Clinic Proceedings

240

261

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“…Systemic administration would be preferable in targeting advanced disease but has usually shown clearly limited efficacy (Berry et al , 2008; Li et al , 2013). Furthermore, preclinical oncolytic virotherapy research in prostate cancer has relied heavily on subcutaneous tumour models due to the high technical demands of orthotopic inoculation.…”

Section: Discussionmentioning

confidence: 99%

Oncolytic alphavirus SFV-VA7 efficiently eradicates subcutaneous and orthotopic human prostate tumours in mice

et al. 2017

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Background:Despite recent therapeutic and diagnostic advances, prostate cancer remains the second leading cause of cancer-related deaths among men in the Western world. Oncolytic viruses that replicate selectively in tumour cells represent a novel treatment candidate for these malignancies.Methods:We analysed infectivity of avirulent Semliki Firest virus SFV-VA7 in human prostate cancer cell lines VCaP, LNCaP and 22Rv1 and in nonmalignant prostate epithelial cell line RWPE-1. Therapeutic potency of SFV-VA7 was evaluated in subcutaneous and orthotopic mouse LNCaP xenograft models.Results:SFV-VA7 infected and killed the tested human prostate cancer cell lines irrespective of their hormone response status, while the nonmalignant prostate epithelial cell line RWPE-1 proved highly virus resistant. Notably, a single peritoneal dose of SFV-VA7 was sufficient to eradicate all subcutaneous and orthotopic LNCaP tumours.Conclusions:Our results indicate that SFV-VA7 is a novel, promising therapeutic virus against prostate cancer warranting further testing in early clinical trials.

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“…We have previously shown that CVA21 is able to rapidly target and lyze a variety of cancer cell types [10][11][12][13][14] expressing high levels of the CVA21 cellular receptors, ICAM-1 and DAF. Herein, the cell surface expression of these receptors was examined in a panel of normal and cancerous breast, colorectal, and pancreatic cell lines.…”

Section: Expression Of Icam-1 and Daf On Cancer Cell Linesmentioning

confidence: 99%

“…One oncolytic virus that is currently under investigation is the wild-type genetically unmodified human enterovirus, Coxsackievirus A21 (CVA21), which induces mild upper respiratory symptoms during natural infection of humans [7][8][9]. Recently, we have shown that CVA21 is an efficient oncolytic agent that specifically targets and rapidly lyzes human malignant melanoma, multiple myeloma, prostate and breast tumors [10][11][12][13][14] expressing upregulated levels of the CVA21 cellular receptors both in vitro and in vivo. In addition, a Phase I clinical trial in late stage melanoma patients has recently been completed, and has demonstrated that intratumorally administered CVA21 (tradename CAVATAK™) is well tolerated in humans, and that 55.55% of patients experienced stabilization or reduction in injected tumor volumes (Smithers and Shafren, unpublished data).…”

Section: Introductionmentioning

confidence: 98%

“…As CVA21 rapidly lyzes a variety of cancer cells both in vitro and in vivo [10][11][12][13][14], the effect of combining CVA21 with commonly used chemotherapeutic agents was investigated. Combination of CVA21 and doxorubicin hydrochloride resulted in synergistically enhanced cytotoxicity in human breast, colorectal, and pancreatic cancer cells when compared to that observed with either agent alone.…”

Section: Introductionmentioning

confidence: 99%

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Enhanced oncolysis mediated by Coxsackievirus A21 in combination with doxorubicin hydrochloride

2010

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Virotherapy is an emerging strategy for the treatment of cancer that utilizes both replication-competent and genetically modified viruses to selectively kill tumor cells. We have previously shown that Coxsackievirus A21 (CVA21), a common-cold producing enterovirus, is an effective oncolytic agent against human melanoma, prostate, and breast cancer xenografts in vivo. CVA21 specifically targets and lytically infects susceptible cells expressing the CVA21 cellular receptors, intercellular adhesion molecule-1 (ICAM-1) and decay-accelerating factor (DAF). Herein, the efficacy of CVA21 administered in combination with doxorubicin hydrochloride as a new therapeutic regimen for cancer was investigated. Flow cytometric analysis demonstrated that the human breast, colorectal, and pancreatic cancer cell lines examined expressed moderate levels of surface ICAM-1 and DAF, whilst a normal breast cell line expressed only minimal levels. When CVA21 was combined with doxorubicin hydrochloride, synergistically enhanced cell death was observed when CVA21 was administered both simultaneously or 24 h prior to doxorubicin hydrochloride exposure. Doxorubicin hydrochloride had no effect on CVA21 replication. Through the use of an orthotopic (MDA-MB-231-luc) xenograft SCID mouse model of human breast cancer we showed that a single intravenous injection of CVA21 in combination with an intraperitoneal injection of doxorubicin hydrochloride resulted in significantly greater tumor reduction compared to either agent alone. Overall, these findings highlight the exciting potential of CVA21, administered in combination with doxorubicin hydrochloride, as a new therapeutic regimen for cancer.

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Potent Oncolytic activity of human enteroviruses against human prostate cancer

Abstract: Enteroviruses CVA21, CVA21-DAFv, and EV1 are potentially potent oncolytic agents against human prostate cancer.

Cited by 40 publications

References 49 publications

Remission of Disseminated Cancer After Systemic Oncolytic Virotherapy

Remission of Disseminated Cancer After Systemic Oncolytic Virotherapy

Oncolytic alphavirus SFV-VA7 efficiently eradicates subcutaneous and orthotopic human prostate tumours in mice

Enhanced oncolysis mediated by Coxsackievirus A21 in combination with doxorubicin hydrochloride

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