Oncolytic viruses in cancer therapy

Abstract

Oncolytic virotherapy is a promising form of gene therapy for cancer, employing nature's own agents to find and destroy malignant cells. The purpose of this review is to provide an introduction to this very topical field of research and to point out some of the current observations, insights and ideas circulating in the literature. We have strived to acknowledge as many different oncolytic viruses as possible to give a broader picture of targeting cancer using viruses. Some of the newest additions to the panel of oncolytic viruses include the avian adenovirus, foamy virus, myxoma virus, yaba-like disease virus, echovirus type 1, bovine herpesvirus 4, Saimiri virus, feline panleukopenia virus, Sendai virus and the non-human coronaviruses. Although promising, virotherapy still faces many obstacles that need to be addressed, including the emergence of virus-resistant tumor cells.

Intravenously usable fully serotype 3 oncolytic adenovirus coding for CD40L as an enabler of dendritic cell therapy

“…1 This leads to the presentation of tumor-associated antigens (TAA) to immunological cells, which results in the activation of antitumor immune responses. 2,3 Importantly, this occurs in the presence of danger signals, which is conducive to immunity versus tolerance.…”

Bovine herpesvirus type 1 as a novel oncolytic virus

“…1,2 Two main forms of oncolytic viruses exist: naturally occurring wild-type oncolytic viruses and modified viruses engineered to achieve selective oncolysis. The collection of gain-of-function or loss-of-function mutations characteristic of a given malignant cancer type will determine the nature of the selective growth advantage over normal cells for an oncolytic virus.…”

“…The collection of gain-of-function or loss-of-function mutations characteristic of a given malignant cancer type will determine the nature of the selective growth advantage over normal cells for an oncolytic virus. 1 For example, many cancer cells are resistant to apoptosis due to gain-of-function mutations in cellular signaling proteins such as Ras. Activated Ras leads to the inhibition of the double-stranded RNA-dependent protein kinase R (PKR), an important factor in the interferon (IFN)-mediated antiviral response.…”

Trial Watch—Oncolytic viruses and cancer therapy

“…[1][2][3][4][5][6] Such an oncotoxic activity (which can be natural or the result of precise genetic manipulations) generally reflect an elevated degree of oncotropism (i.e., the ability of some viruses to preferentially enter neoplastic cells over normal cells of the same type), 7-9 and/or the pronounced susceptibility of some cancer cells to viral replication as such, 2,[10][11][12] or to the expression of (endogenous or exogenous) cytotoxic gene products. 1,2,13 Importantly, preclinical and clinical observations accruing over the past decade indicate that the therapeutic activity of oncolytic viruses cannot be ascribed solely to oncolysis, but rather involves the activation of an adaptive, tumor-targeting immune response. [14][15][16][17][18][19] Conversely, antiviral immunity (be it innate or adaptive) often constitutes an obstacle against the efficacious implementation of oncolytic virotherapy in cancer patients, mostly because it sequesters or neutralizes viral particles before they reach malignant lesions.…”