Abstract
Various viruses have been studied and developed for oncolytic virotherapies. In virotherapy, a relatively small amount of viruses used in an intratumoral injection preferentially replicate in and lyse cancer cells, leading to the release of amplified viral particles that spread the infection to the surrounding tumor cells and reduce the tumor mass. Adenoviruses (Ads) are most commonly used for oncolytic virotherapy due to their infection efficacy, high titer production, safety, easy genetic modification, and well-studied replication characteristics. Ads with deletion of E1b55K preferentially replicate in and destroy cancer cells and have been used in multiple clinical trials. H101, one of the E1b55K-deleted Ads, has been used for the treatment of late-stage cancers as the first approved virotherapy agent. However, the mechanism of selective replication of E1b-deleted Ads in cancer cells is still not well characterized. This review will focus on three potential molecular mechanisms of oncolytic replication of E1b55K-deleted Ads. These mechanisms are based upon the functions of the viral E1B55K protein that are associated with p53 inhibition, late viral mRNA export, and cell cycle disruption.
Highlights
Cancer is the most common cause of death in the world [1]
The original hypothesis was that, since many cancer cells lack functional p53 protein or its pathways, the E1B55K function of inhibiting p53 is not as important as it is in normal cells, and E1b55K-deleted Ads could selectively replicate in cancer cells with p53 deficiency or dysfunctional pathways
The second mechanism is that cancer cells have a propensity to support the nuclear export of viral late mRNAs in the absence of the E1B55K protein, and allow the oncolytic replication of E1b55K-deleted Ads
Summary
The limitations of currently available therapies demand development of more potent cancer treatment options. Oncolytic virotherapy represents a fast-growing therapeutic platform for cancer treatment [2,3]. The therapeutic effects emanate from a relatively small amount of viruses that preferentially replicate in and lyse cancer cells, followed by a localized spread of viral infection to the surrounding tumor cells, leading to reduction of the tumor mass [4]. Many viruses have been developed, Ads are still the most commonly used for oncolytic virotherapy due to their infection efficacy, high titer production, safety, easy genetic modification, and well-studied replication characteristics [6]. This review will focus on molecular mechanisms of the selective replication of E1b-deleted Ads in cancer cells
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