Oncolytic virotherapy with an HSV amplicon vector expressing granulocyte–macrophage colony-stimulating factor using the replication-competent HSV type 1 mutant HF10 as a helper virus

Abstract

Direct viral infection of solid tumors can cause tumor cell death, but these techniques offer the opportunity to express exogenous factors to enhance the antitumor response. We investigated the antitumor effects of a herpes simplex virus (HSV) amplicon expressing mouse granulocyte-macrophage colony-stimulating factor (mGM-CSF) using the replication-competent HSV type 1 mutant HF10 as a helper virus. HF10-packaged mGM-CSF-expressing amplicon (mGM-CSF amplicon) was used to infect subcutaneously inoculated murine colorectal tumor cells (CT26 cells) and the antitumor effects were compared to tumors treated with only HF10. The mGM-CSF amplicon efficiently replicated in CT26 cells with similar oncolytic activity to HF10 in vitro. However, when mice subcutaneously inoculated with CT26 cells were intratumorally injected with HF10 or mGM-CSF amplicon, greater tumor regression was seen in mGM-CSF amplicon-treated animals. Furthermore, mGM-CSF amplicon treatment prolonged mouse survival. Immunohistochemical analysis revealed increased inflammatory cell infiltration in the solid tumor in the mGM-CSF amplicon-treated animals. These results suggest that expression of GM-CSF enhances the antitumor effects of HF10, and HF10-packaged GM-CSF-expressing amplicon is a promising agent for the treatment of subcutaneous tumors.

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

“…The current mainstream methods for cancer treatment are novel biological therapeutics, and oncolytic viruses are one type of biological therapeutic that appear to have a wide spectrum of anticancer activity with minimal human toxicity. Because the clinical effects of oncolytic virus therapy are strongly related to the host immune system, we have examined the effects of HF10 injections in conjunction with another immune stimulus, such as Granulocyte-macrophage colony stimulating factor, to improve the efficacy of oncolytic virus therapy, 27 We believe that further development of oncolytic virus therapy and HF10 will be a promising therapeutic method that should be examined in a robust clinical study.…”

Abnormal expression of TRIB3 in colorectal cancer: a novel marker for prognosis

“…The incidence of colorectal cancer (CRC) has increased significantly in recent years, in concert with the changing lifestyle (Kohno et al, 2007). The major cause of death in CRC is liver metastases (Yamasaki et al, 2007).…”

ATP11A is a novel predictive marker for metachronous metastasis of colorectal cancer

“…In Japan, the incidence of colorectal cancer (CRC) has significantly increased in recent years with changes in lifestyle (1). CRC is now one of the most important causes of death from neoplastic disease in Japan (1). The necessity of intensive follow-up and adjuvant therapy for CRC has been recently proposed in view of predicting recurrence and metastasis in curative surgical resection cases (2)(3)(4).…”

“…In Japan, the incidence of colorectal cancer (CRC) has significantly increased in recent years with changes in lifestyle (1). CRC is now one of the most important causes of death from neoplastic disease in Japan (1).…”