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The review that set the modern agenda for cancer-killing viruses, and named the four things that had to be solved.
Russell, Peng and Bell review oncolytic virotherapy as replication-competent viruses used to destroy cancers. They summarise preclinical proof of feasibility for a single-shot cure, drugs that accelerate spread of virus within a tumour, strategies to maximise the immunotherapeutic action of the virus, and clinical confirmation of a critical concentration of virus in the blood below which vascular delivery and intratumoural replication do not happen.
The value of the paper is that it states the field's problems rather than its promise: choosing between a proliferating number of platforms and engineered derivatives, transiently suppressing and then unleashing the immune system so that both virus spread and antitumour immunity are maximised, building preclinical models that mean something, and manufacturing virus at yields orders of magnitude higher than were then possible. Every one of those four remains open.
Read against what happened next, this review is a fair scorecard. The immune timing problem, the delivery threshold and the manufacturing yield are still the reasons most programmes fail, and the proliferation of platforms the authors warned about is still the reason the field has many products and few randomised wins.
Shares Stephen J. Russell, Oncolytic viruses.
Shares John C. Bell, Oncolytic viruses.
Shares Stephen J. Russell, Oncolytic viruses.
Shares Stephen J. Russell, Oncolytic viruses.
Shares John C. Bell, Oncolytic viruses.