%0 Journal Article
%T Oncolytic Immunotherapy: Where Are We Clinically?
%A Akseli Hemminki
%J Scientifica
%D 2014
%I Hindawi Publishing Corporation
%R 10.1155/2014/862925
%X Following a century of preclinical and clinical work, oncolytic viruses are now proving themselves in randomized phase 3 trials. Interestingly, human data indicates that these agents have potent immunostimulatory activity, raising the possibility that the key consequence of oncolysis might be induction of antitumor immunity, especially in the context of viruses harboring immunostimulatory transgenes. While safety and efficacy of many types of oncolytic viruses, including adenovirus, herpes, reo, and vaccinia seem promising, few mechanisms of action studies have been performed with human substrates. Thus, the relative contribution of ˇ°pureˇ± oncolysis, the immune response resulting from oncolysis, and the added benefit of adding a transgene remain poorly understood. Here, the available clinical data on oncolytic viruses is reviewed, with emphasis on immunological aspects. Since the ˇ°War on Cancerˇ± was launched in the 1970s, the treatment of most cancers has improved steadily. Nevertheless, most metastatic solid tumors remain incurable. Therefore, new agents with novel mechanisms of action and lacking cross-resistance to the currently available approaches are needed. Due to hypothetical safety concerns, cancer gene therapy approaches have traditionally been based on viruses that are unable to replicate. Although such ˇ°vectorsˇ± have provided high preclinical efficacy and good clinical safety data, trials have suggested that their efficacy may be limited when faced with advanced and bulky disease, because of limited penetration from the needle tract into further area of the tumor. Nevertheless, in the context of local disease, even replication deficient viruses could have their uses when combined optimally to routine therapies [1, 2]. In the context of cancer therapy, nonreplicating viruses have largely been abandoned in favor of replication competent platforms, since there are few advantages to the former, as safety of the latter has proven excellent. Moreover, one could argue that there are few caveats to arming a virus, over an unarmed virus, assuming that the arming device adds to efficacy. Thus, armed replication competent viruses are now the most popular cancer gene therapy approach. Viruses featuring selective replication in tumor cells, also known as oncolytic viruses, can improve penetration of and dissemination within solid tumor masses [3¨C5]. Emerging data also suggests their ability to reach distant metastases through vasculature, following release from dying tumor cells [6]. One of the first events during virus replication is amplification of
%U http://www.hindawi.com/journals/scientifica/2014/862925/