A phase I dose-escalation clinical trial of intraoperative direct intratumoral injection of HF10 oncolytic virus in non-resectable patients with advanced pancreatic cancer

Nakao, Akimasa; Kasuya, Hideki; Sahin, Tevfik Tolga; Nomura, Naohiro; Kanzaki, Akiyuki; Misawa, Makoto; Shirota, Takashi; Yamada, Suguru; Fujii, Tsutomu; Sugimoto, Hiroyuki; Shikano, Takaaki; Nomoto, Shuji; Takeda, Shin; Kodera, Yasuhiro; Nishiyama, Yukihiro

doi:10.1038/cgt.2010.65

Cited by 116 publications

(79 citation statements)

References 24 publications

(28 reference statements)

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“…At the clinical level it was of note that intratumorally injected ONYX-15 OV combined with gemcitabine was well-tolerated in a phase I/II clinical trial of patients with pancreatic cancer (10). The HSV-1 OV, HF10, reached the clinic and was well tolerated in phase I trials (11) while a clinical trial with the HSV-1-based OV, BioVex GMCSF, is running (12). Thus, despite the severity of the disease and the certain success of OVs in preclinical trials, only very few of them reached the clinics.…”

Section: Introductionmentioning

confidence: 99%

A Novel CDC25B Promoter–Based Oncolytic Adenovirus Inhibited Growth of Orthotopic Human Pancreatic Tumors in Different Preclinical Models

Weber

Gidekel

Werbajh

et al. 2015

Clinical Cancer Research

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Purpose: We decided to construct a novel oncolytic adenovirus whose replication was driven by the CDC25B promoter for its use in preclinical models of pancreatic cancer.Experimental Design: We placed the essential E1A gene under control of the CDC25B promoter. Based on preliminary data, we pseudotyped the adenovirus with a chimeric fiber of serotypes 5/3. We investigated the in vitro lytic effect and the in vivo therapeutic efficacy in combination with gemcitabine on human pancreatic tumor xenografts orthotopically growing in nude mice and in tumors growing in Syrian hamsters. We also assessed biochemical markers of hepatic toxicity and CA19.9 levels.Results: AV25CDC exhibited a strong in vitro lytic effect on pancreatic cancer cells. In vivo administration of AV25CDC combined with gemcitabine in mice harboring subcutaneously growing SW1990 pancreatic tumors almost abrogated tumor growth.Nude mice harboring 15-day-old orthotopic tumors, treated intratumorally or systemically with AV25CDC combined with gemcitabine, exhibited 70% to 80% reduction in tumor size compared with control mice that lasted for at least 60 days. Chemovirotherapy treatment induced a return to normal levels of biochemical parameters of hepatic toxicity; these mice exhibited more than 90% reduction in CA19.9 serum levels compared with control. Chemovirotherapy efficacy was confirmed in mice harboring Mia PaCa-2 tumors and in Syrian hamster harboring HaP-T1 tumors. We observed that viral treatment disrupted tumor architecture and induced an increase in MMP-9 activity that might facilitate gemcitabine penetrability.Conclusion: These data demonstrate that AV25CDC is an effective oncolytic agent candidate for pancreatic cancer chemovirotherapy combination.

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Section: Introductionmentioning

confidence: 99%

A Novel CDC25B Promoter–Based Oncolytic Adenovirus Inhibited Growth of Orthotopic Human Pancreatic Tumors in Different Preclinical Models

Weber

Gidekel

Werbajh

et al. 2015

Clinical Cancer Research

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“…Although other types of HSV viruses have been used in intraoperative injection of pancreatic tumors (32), HSV has also showed promise when injected into tumors via EUS. An example of this is OncoVex GM-CSF, which has a deletion that makes it selective to tumor cells.…”

Section: Herpes Virusmentioning

confidence: 99%

Endoscopic ultrasound in pancreatic cancer: innovative applications beyond the basics

Yoo¹,

Kistler²,

Yan³

et al. 2016

J. Gastrointest. Oncol.

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Endoscopic ultrasound (EUS) has become a mainstay in assisting in the diagnosis and staging of pancreatic cancer. In addition, EUS provides a modality to treat chronic pain through celiac plexus neurolysis. Currently, there is growing data and utilization of EUS in more diverse and innovative applications aimed at providing more sophisticated diagnostic, prognostic and therapeutic options for patients with pancreatic cancer. EUS delivery of chemotherapy, viral and biological vectors and fiducial markers may eventually revolutionize the way clinicians approach the care of a patient with pancreatic cancer. J Gastrointest Oncol 2016;7(6):1019-1029 jgo.amegroups.com pancreatic tumor, thus preventing side effects of systemic chemotherapy. It also allows for a more comprehensive realtime image, a shorter puncture pathway, and a lower risk of complications when compared to via computed tomography (CT) or abdominal ultrasound (US)-guided procedures.EUS-guided fine needle injections (EUS-FNIs) were initially studied in a porcine model where they injected paclitaxel into the pancreas; clinically detectable concentrations of the drug could not be detected beyond a distance of 30-50 mm from the injection site (6). Levy et al. studied EUS-FNI of gemcitabine in patients with unresectable cancer and demonstrated that several patients were able to be down staged and undergo subsequent resection (7). EUS-FNI of chemotherapy can be limited by the high density of fibrosis in pancreatic cancer, making it difficult to pierce the needle into the pancreatic tumor, and make it challenging to inject adequate amounts of an injected solution into the mass (7). Although interventional EUS has not been shown to significantly improve the survival rate and prolong the survival time in patients with pancreatic cancer, it can effectively induce tumor cell death. Additional studies are needed to further explore this therapeutic application in the future. EUS in predicting prognosis and response to chemotherapyIn addition to the potential for directly administering chemotherapy, assessing the prognosis and response to therapy is another developing role for EUS. Currently, many academic institutions and industry trials have adopted the response evaluation criteria in solid tumors (RECIST) criteria to help standardize the assessment of prognosis and response to therapies (8). RECIST criteria are largely based on radiographic cross-sectional imaging. It has been proposed that tumor response to neoadjuvant chemotherapy (defined by the RECIST criteria) would be required prior to surgery for borderline resectable pancreatic tumors. However, in a study by Katz et al. only 12% of cases had radiographic changes associated with neoadjuvant chemotherapy that met the RECIST criteria (9). Furthermore, only one patient out of 129 patients had enough of a reduction in tumor size to be reclassified as resectable via radiographic criteria, and yet 60% of those patients underwent surgical resection, suggesting that surgical resection in patients with bor...

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“…HF10 replicates more efficiently with low virulence than wild-type HSV-1. Its safety and effectiveness are tested in many animal models, and it has been used for treatment of breast cancer, malignant melanoma and pancreatic cancer in clinical trial [38][39][40][41]. Recent report showed that HF10 also had effects on the tumor microenvironment in patients with recurrent carcinoma tumor [42].…”

Section: An Overview Of Hsvmentioning

confidence: 99%

Advance in herpes simplex viruses for cancer therapy

Liu

Dai

You

et al. 2013

Sci. China Life Sci.

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Oncolytic virotherapy is an attractive approach that uses live viruses to selectively kill cancer cells. Oncolytic viruses can be genetically engineered to induce cell lyses through virus replication and cytotoxic protein expression. Herpes simplex virus (HSV) has become one of the most widely clinically used oncolytic agent. Various types of HSV have been studied in basic or clinical research. Combining oncolytic virotherapy with chemotherapy or radiotherapy generally produces synergic action with unclear molecular mechanisms. Arming HSV with therapeutic transgenes is a promising strategy and can be used to complement conventional therapies. As an efficient gene delivery system, HSV has been successfully used to deliver various immunomodulatory molecules. Arming HSV with therapeutic genes merits further investigation for potential clinical application.

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A phase I dose-escalation clinical trial of intraoperative direct intratumoral injection of HF10 oncolytic virus in non-resectable patients with advanced pancreatic cancer

Cited by 116 publications

References 24 publications

A Novel CDC25B Promoter–Based Oncolytic Adenovirus Inhibited Growth of Orthotopic Human Pancreatic Tumors in Different Preclinical Models

A Novel CDC25B Promoter–Based Oncolytic Adenovirus Inhibited Growth of Orthotopic Human Pancreatic Tumors in Different Preclinical Models

Endoscopic ultrasound in pancreatic cancer: innovative applications beyond the basics

Advance in herpes simplex viruses for cancer therapy

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