Use of cell fusion proteins to enhance adenoviral vector efficacy as an anti-cancer therapeutic (original) (raw)

2020, Cancer Gene Therapy

Oncolytic viruses are designed to replicate in and kill cancer cells, and have shown tremendous promise in preclinical and clinical studies. Indeed, several oncolytic viruses are available to patients in a number of different countries around the world. However, most oncolytic viruses show a poor ability to spread throughout the tumor mass, frequently leading to only a partial response and regrowth of the tumor. One approach to improve spread of the viral effect throughout the tumor mass is to arm the oncolytic virus with a fusogenic protein. In this manner, a single infected cell can fuse with many adjacent uninfected cells, essentially amplifying the anti-tumor effects. In this review, we discuss the development and use of fusogenic proteins to enhance the efficacy of human adenovirus-based vectors for cancer therapy. Approximately 40% of the human population will receive a diagnosis of cancer within their lifetime [1]. Conventionally, cancer is treated with surgery, chemotherapy and radiation therapy; however, these treatments are associated with poor prognosis, and about half of all diagnosed patients will succumb to the disease [2]. The high mortality rate associated with cancer highlights the need for development of more effective therapies. This review will focus on the problems and prospects of human adenovirus (HAdV)-based vectors for cancer therapy, specifically focusing on a class of HAdV-based therapeutics that express fusion proteins. Such vectors can circumvent one of the main problems associated with traditional HAdV vectors, poor spread throughout a solid tumor mass, which may lead to greater therapeutic efficacy.

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