Oncolytic vaccinia virus armed with the endostatin‐angiostatin fusion protein; a novel therapy for head and neck cancer

Abstract

Objectives. The survival of patients with head and neck squamous cell carcinoma (HNSCC) has not improved significantly over recent decades. This had lead to the development of new therapies. Oncolytic viral therapy is a promising new strategy for cancer treatment. The first oncolytic virus licensed for treatment was an adenovirus for HNSCC.1 However, the outcomes of clinical trials using viral monotherapy have been disappointing. Oncolytic vaccinia virus represents an attractive alternative as its replication is less dependent than adenovirus on the genetic make‐up of host cells and it has been used safely as the smallpox vaccine in millions of patients.2Method. This study evaluated the potential of vaccinia virus as a treatment for HNSCC in vitro and in human xenograft models in vivo.Results. The Lister strain of vaccinia virus was more potent than adenovirus against all tumour cells tested in vitro. The virus displayed high selectivity for cancer cells, sparing normal cells both in vitro and in vivo. In order increase antitumour potency, a novel vaccinia virus expressing the endostatin–angiostatin fusion protein was constructed. This inhibits new blood vessel formation as well as tumour growth by oncolysis. The protein was both expressed in virus‐infected tumour cells and demonstrated function by the inhibition of human umbilical vein epithelial cell proliferation and tube formation in vitro.Conclusions. This novel vaccinia virus is a promising therapeutic agent for HNSCC, which requires further evaluation in vivo.References. 1 Garber K. (2006) China approves world's first oncolytic virus therapy for cancer treatment. J. Natl. Cancer Inst. 98, 298–3002 Thorne S.H., Bartlett D.L. & Kirn D.H. (2005) The use of oncolytic vaccinia viruses in the treatment of cancer: a new role for an old ally? Curr. Gene Ther. 5, 429–443