Pilot Study of Oncolytic Viral Therapy Using Mutant Herpes Simplex Virus (HF10) Against Recurrent Metastatic Breast Cancer

Kimata, Hideaki; Imai, Tsuneo; Kikumori, Toyone; Teshigahara, Osamu; Nagasaka, Tetsuro; Goshima, Fumi; Nishiyama, Yukihiro; Nakao, Akimasa

doi:10.1245/aso.2006.08.035

Cited by 76 publications

(66 citation statements)

References 16 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…20 During the follow-up period, we observed a 30À70% reduction in the size of the tumors treated with HF10.…”

Section: Resultsmentioning

confidence: 79%

“…The genome and genetic alterations of this herpes simplex virus are summarized in Figure 1. 20 Briefly, the virus carries two main genetic alterations; (i) a 3832-bp deletion leading to loss of the UL56 promoter, making the gene dysfunctional; and (ii) near the terminal redundance sequence in long arm (TRL) end of the genome, a 6027-bp segment is present in an inverted orientation. The loss of UL56 function is the major functional alteration.…”

Section: Hf10 Virusmentioning

confidence: 99%

“…Previously, we published a promising preliminary clinical study demonstrating the efficacy of HF10 in patients with recurrent breast cancers or unresectable pancreatic carcinoma. 20,21 The power of HF10 lies in the fact that it is a spontaneous mutant and is genetically very similar to the parental virus.…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Impact of novel oncolytic virus HF10 on cellular components of the tumor microenviroment in patients with recurrent breast cancer

et al. 2011

View full text Add to dashboard Cite

Oncolytic viruses are a promising method of cancer therapy, even for advanced malignancies. HF10, a spontaneously mutated herpes simplex type 1, is a potent oncolytic agent. The interaction of oncolytic herpes viruses with the tumor microenvironment has not been well characterized. We injected HF10 into tumors of patients with recurrent breast carcinoma, and sought to determine its effects on the tumor microenvironment. Six patients with recurrent breast cancer were recruited to the study. Tumors were divided into two groups: saline-injected (control) and HF10-injected (treatment). We investigated several parameters including neovascularization (CD31) and tumor lymphocyte infiltration (CD8, CD4), determined by immunohistochemistry, and apoptosis, determined by terminal deoxynucleotidyl transferase dUTP nick end labeling assay. Median apoptotic cell count was lower in the treatment group (P ¼ 0.016). Angiogenesis was significantly higher in treatment group (P ¼ 0.032). Count of CD8-positive lymphocytes infiltrating the tumors was higher in the treatment group (P ¼ 0.008). We were unable to determine CD4-positive lymphocyte infiltration. An effective oncolytic viral agent must replicate efficiently in tumor cells, leading to higher viral counts, in order to aid viral penetration. HF10 seems to meet this criterion; furthermore, it induces potent antitumor immunity. The increase in angiogenesis may be due to either viral replication or the inflammatory response.

show abstract

“…20 During the follow-up period, we observed a 30À70% reduction in the size of the tumors treated with HF10.…”

Section: Resultsmentioning

confidence: 79%

Section: Hf10 Virusmentioning

confidence: 99%

See 1 more Smart Citation

Impact of novel oncolytic virus HF10 on cellular components of the tumor microenviroment in patients with recurrent breast cancer

et al. 2011

View full text Add to dashboard Cite

show abstract

“…In contrast to our former clinical trial on recurrent breast cancer, 12 the present clinical trial on pancreatic cancer required that we inject the therapeutic virus into the organ during the laparotomy or with computed tomography (CT)-guided injection, although there is a possibility of venous injections with in vivo studies. 14 Therefore, we chose to inject the virus during the laparotomy when the cancer was classified as non-resectable.…”

Section: Methodsmentioning

confidence: 99%

“…Pathological analyses revealed virus inclusion bodies in the specimen that were resected after 2 weeks of virus injection. 12 In addition, tests performed at the department of Oto-Rhino-Laryngology revealed highly concentrated CD4 þ and CD8 þ cell clusters in the tumor. Recently, it was determined that part of the tumor-killing effects of oncolytic virus therapy depends on the host immune response.…”

Section: Introductionmentioning

confidence: 98%

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

et al. 2010

View full text Add to dashboard Cite

In 2005, we initiated a clinical trial that examined the efficacy of the oncolytic virus HF10 to treat pancreatic cancer. Pancreatic cancer continues to have a high mortality rate, despite multimodal treatments for patients, and new therapeutic methods are greatly needed. The current mainstream methods for cancer treatment include biological therapeutics such as trastuzumab (Herceptin) for breast cancer or erlotinib (Tarceva) for non-small cell lung cancer. Oncolytic virus therapy is a new and promising treatment strategy for cancer. Oncolytic viruses are novel biological therapeutics for advanced cancer that appear to have a wide spectrum of anticancer activity with minimal human toxicity. To examine the efficacy of oncolytic virus therapy for pancreatic cancer, we initiated pilot studies by injecting six patients with non-resectable pancreatic cancer with three doses of HF10. All patients were monitored for 30 days for local and systemic adverse effects and were not administered any other therapeutics during this period. There were no adverse side-effects, and we observed some therapeutic potential based on tumor marker levels, survival, pathological findings and diagnostic radiography. The tumors were classified as stable disease in three patients, partial response in one patient and progressive disease in two patients.

show abstract

Engineering Herpes Simplex Virus for Cancer Oncolytic Virotherapy

Buhrman

Cheema

Fulci

2010

Emerging Cancer Therapy

View full text Add to dashboard Cite

Pilot Study of Oncolytic Viral Therapy Using Mutant Herpes Simplex Virus (HF10) Against Recurrent Metastatic Breast Cancer

Abstract: This pilot study found HF10 to be safe and effective against metastatic breast cancer.

Cited by 76 publications

References 16 publications

Impact of novel oncolytic virus HF10 on cellular components of the tumor microenviroment in patients with recurrent breast cancer

Impact of novel oncolytic virus HF10 on cellular components of the tumor microenviroment in patients with recurrent breast cancer

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

Engineering Herpes Simplex Virus for Cancer Oncolytic Virotherapy

Contact Info

Product

Resources

About