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Review
. 2016 Dec:21:9-15.
doi: 10.1016/j.coviro.2016.06.009. Epub 2016 Jul 2.

Recent advances in oncolytic adenovirus therapies for cancer

Amanda Rosewell Shaw  1 , Masataka Suzuki  2
Affiliations
Review

Recent advances in oncolytic adenovirus therapies for cancer

Amanda Rosewell Shaw et al. Curr Opin Virol. 2016 Dec.

Abstract

Oncolytic adenoviruses (Onc.Ads) selectively replicate in and lyse cancer cells and are therefore commonly used vectors in clinical trials for cancer gene therapy. Building upon the well-characterized adenoviral natural tropism, genetic modification of Onc.Ad can enhance/regulate their transduction and replication within specific cancer cell types. However, Onc.Ad-mediated tumor cell lysis cannot fully eliminate tumors. The hostile tumor microenvironment provides many barriers to efficient oncolytic virotherapy, as tumors develop structure and immune-evasion mechanisms in order to grow and ultimately spread. For these reasons, Onc.Ads modified to deliver structural or immune modulatory molecules (Armed Onc.Ads) have been developed to overcome the physical and immunological barriers of solid tumors. The combination of oncolysis with tumor microenvironment modulation/destruction may provide a promising platform for Ad-based cancer gene therapy.

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Figures

Figure 1
Figure 1. The inhibitory tumor microenvironment
The tumor microenvironment is heterogeneous, consisting not only of malignant cells but also a wide range of cellular and non-cellular components that contribute to cancer progression. Although Onc.Ads can cause cancer cell lysis resulting in some anti-tumor effects, in order to eliminate the tumor Onc.Ads need to target a variety of other tumor-associated factors within the microenvironment. Accumulation of cancer associated fibroblasts, dense extracellular matrix, and formation of neovasculature promote the growth of the tumor and also impede the dissemination of Onc.Ads throughout the entire tumor mass. Areas of the tumor are often hypoxic and this also inhibits viral replication. While Onc.Ad-mediated cancer cell lysis can lead to immune activation by releasing damage-associated molecular patterns (DAMPs) and tumor neoantigens, the tumor microenvironment often contains inhibitory immune cells such as Tregs, MDSCs, and M2 macrophages, which counteract the immune stimulatory advantages of Onc.Ads.
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