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

Abstract

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.

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Fig. 2: CRAd armed with p14 FAST protein for cancer therapy.

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Acknowledgements

Funding was provided by grants to R.J.P. from the Cancer Research Society (grant number 19363), Canadian Institutes of Health Research (MOP-136898, MOP-142316) and the Natural Sciences and Engineering Research Council (RGPIN-2014-04810, RGPIN-2019-04786). R.C. and J.D.P. were supported by the Ontario Government through a Queen Elizabeth II Graduate Scholarship in Science and Technology and an Ontario Graduate Scholarship.

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Del Papa, J., Clarkin, R.G. & Parks, R.J. Use of cell fusion proteins to enhance adenoviral vector efficacy as an anti-cancer therapeutic. Cancer Gene Ther (2020). https://doi.org/10.1038/s41417-020-0192-9

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