Significant progress has been made in cancer therapies in the past few decades, however, the mortality rates for most malignancies and the inhibition of cancer growth and progression are still significant challenges. The conventional regimen of cancer therapies, such as chemotherapy and radiotherapy, have a limited therapeutic index and a large of treatment-related drug resistance and severe side effects. This situation provides an impetus for the development of novel therapeutic strategies for the treatment of cancer, which is more selective and specific. With a better understanding of cancer biology and virology, oncolytic virus therapy is becoming a promising treatment modality for tumor targeting and offers unique opportunities for tumor therapy.
Oncolytic virus therapy originated early in the last century. It began with the observation of occasional tumors spontaneously shrink or regressions after the inoculation of an attenuated rabies vaccine in cancer patients in 1912. The concept of using an oncolytic virus for tumors therapy dated back to nearly over a century. Based on molecular biology and virology, the development of oncolytic viruses as cancer therapy has expanded rapidly and made significant progress over the past few decades.
In contrast to gene therapy, where a virus is used as a mere carrier for transgene delivery, oncolytic virus therapy employs the virus itself as an active drug reagent to find and destroy malignant cells. Oncolytic virus therapy is based on the definition of oncolytic viruses that can selectively infect and destroy the malignant tumor cells with little or no toxicities to normal cells and allows higher and effective drug doses to reach each tumor cell. The superiority of oncolytic virus therapy relative to other approaches relies on its specificity against tumor cells but only limited pathogenicity to normal tissue, and the ability of oncolytic virus engineering with increased tumor selectivity and enhanced oncolytic activity. A widely-recognized feature regarding oncolytic virus therapy is that a systemic tumor‐specific immunity is efficiently induced in the course of oncolytic activities. This is expected to play a significant role in prolonging the survival of cancer patients.
Fig.1 Mechanisms of oncolytic-virus-based cancer therapy. (Lee, 2018)
Oncolytic viruses have the specificity against tumor cells and not exclusively for targeting replicating cells. Oncolytic viruses can potentiate or restore already existing but weak antitumor immunity or induce a novel antigen response. Besides, the antitumor activity of oncolytic viruses can be increased by arming with therapeutic genes. These viral therapies have been shown to emerging as a novel therapeutic class and related to multiple mechanisms such as the mechanisms of immunosurveillance, mechanisms of tumor escape, immunomodulatory mechanisms, mechanisms of oncolytic virus destroying tumor cells, mechanisms of oncolytic virus targeting tumor cells, and vaccine mechanism of oncolytic virus therapy.
Currently, oncolytic viruses are better tolerated and shown strong tumor-reducing effects against many types of specific cancers. The clinical development of oncolytic viral therapy has accelerated in the last few years, and numerous oncolytic viruses have entered clinical trials for a variety of cancers. The increasing results demonstrate the potential promise of this approach for the treatment of human and animal cancers. Oncolytic virus therapy has comparable or superior effectiveness in achieving antitumor responses and can be delivered through a combination of different approaches. Because induction of specific antitumor immunity in the course of oncolytic activities is the common feature that plays an essential role in presenting antitumor effects, the efficacy of oncolytic virus therapy is expected to improve further when combined with immunotherapy. Additionally, by arming oncolytic viruses with functional therapeutic transgenes, a whole panel of oncolytic viruses with a variety of antitumor functions would be available and expected to produce major therapeutic effects for cancers according to their types and stages.
Taking advantage of our OncoVirapy™ platform and over a decade of experience in oncolytic virus therapy development, Creative Biolabs can provide high-quality oncolytic virus-based therapy development to our customers all over the world.
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