Abstract
Oncolytic adenovirus (Ad) vectors present a new modality to treat cancer. These vectors attack tumors via replicating in and killing cancer cells. Upon completion of the vector replication cycle, the infected tumor cell lyses and releases progeny virions that are capable of infecting neighboring tumor cells. Repeated cycles of vector replication and cell lysis can destroy the tumor. Numerous Ad vectors have been generated and tested, some of them reaching human clinical trials. In 2005, the first oncolytic Ad was approved for the treatment of head-and-neck cancer by the Chinese FDA. Oncolytic Ads have been proven to be safe, with no serious adverse effects reported even when high doses of the vector were injected intravenously. The vectors demonstrated modest anti-tumor effect when applied as a single agent; their efficacy improved when they were combined with another modality. The efficacy of oncolytic Ads can be improved using various approaches, including vector design, delivery techniques, and ancillary treatment, which will be discussed in this review.
Highlights
In spite of tremendous advances in the prevention, diagnosis, and therapy of cancer, it is the second most frequent cause of mortality in the United States
The first group of vectors has the same e1b-55K deletion as ONYX-015 and express a fusion protein consisting of a cytosine deaminase (CD) and herpes simplex virus thymidine kinase (TK) prodrugconverting enzymes
It has been shown that intravenous administration of an oncolytic Ad can be efficacious [52], the liver tropism of oncolytic Ads is widely believed to be a hindrance for systemic delivery of the vector; besides the liver toxicity, the anti-viral efficacy decreases because only a fraction of the vector reaches the intended target
Summary
In spite of tremendous advances in the prevention, diagnosis, and therapy of cancer, it is the second most frequent cause of mortality in the United States. Many forms of cancers are considered to be incurable, and treatment for many tumors results in only a minor increase in the time of survival These treatment regimes cause serious side effects; some patients decide to receive palliative. It is not surprising that researchers continuously work to develop new modalities for anti-cancer therapy One such new method uses genetically modified oncolytic (replication-competent, RC) adenovirus (Ad) “vectors” [1]. The replication of the virus and its effect on the host cell and the host immune system have been examined in great detail It is known from decades of basic research with Ads that the virus is genetically stable, and methods for engineering Ad vectors and producing of large quantities of high-titer stocks have been established. Some oncolytic Ads embody a combination of these methods to achieve more stringent control of replication
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