Update on oncolytic viral therapy – targeting angiogenesis

Abstract

Oncolytic viruses (OVs) have the ability to selectively replicate in and lyse cancer cells. Angiogenesis is an essential requirement for tumor growth. Like OVs, the therapeutic effect of many angiogenesis inhibitors has been limited, leading to the development of more effective approaches to combine antiangiogenic therapy with OVs. Angiogenesis can be targeted either directly by OV infection of vascular endothelial cells, or by arming OVs with antiangiogenic transgenes, which are subsequently expressed locally in the tumor microenvironment. In this review, we describe the development and targeting of OVs, the role of angiogenesis in cancer, and the progress made in arming viruses with antiangiogenic transgenes. Future developments required to optimize this approach are addressed.

“Right-to-Try” experimental drugs: an overview

“…On the other hand, China for almost two decades approved a number of experimental drugs. From 2003 to 2005, the SFDA approved H101, experimental oncolytic viral therapy for head and neck cancer, an angiogenic Endostar inhibitor for treating non-small cell lung cancer and Gendicine for treating head and neck cancer [9][10][11]. However, in December, 2019, the Drug Administration Law (DAL) by the SFDA came into effect [12].…”

Prospects for combined use of oncolytic viruses and CAR T-cells

“…Furthermore, OVs have been armed with anti-angiogenic chemokines such as platelet factor 4 or the angiostatic C-X-C motif chemokines CXCL-10 and CXCL-12. A plethora of endogenous anti-angiogenic molecules have also been explored in recombinant OVs including endostatin, angiostatin, vasculostatin, plasminogen kringle 5, canstastin and the fibroblast growth factor receptor (FGFR) [ 204 ]. As yet, these anti-angiogenic OVs have not been explored in combination with ACT and it is unclear whether this approach may be replicated by the systemic delivery of anti-angiogenic agents already licensed for the treatment of solid tumours such as the anti-VEGFA mAb bevacizumab or the anti-VEGFR2 mAb, ramucirumab.…”

Gene Therapy in Head and Neck Cancer

“…Attempts have been made to inhibit tumor growth and metastasis by blocking the process of angiogenesis with gene therapy. Recently oncolytic viruses have been armed with antiangiogenic factors such as endostatin/angiostatin [19] . Thus the gene therapy treatment strategies may include replacement of defective tumor suppressor genes, inactivation of oncogenes, stimulating the immune response and targeting tumor vasculature to avoid angiogenesis.…”