Oncolytic Virus Engineering: The Future Key for Cancer Treatmen

  • Oncolytic virus (OV) is a type of virus that can selectively infect and kill cancer cells. When infected cancer cells are destroyed by oncolysis, OVs continue to release new infectious virus particles to help destroy the remaining tumors without harming healthy tissue. Oncolytic viruses can not only cause direct destruction of tumor cells but also effectively induce immune responses to the infected tumor cells. OVs can generally be classified into two major categories: natural viruses and genetically modified virus strains.


    Natural viruses include wild-type and natural variants of weak viruses. For example, reovirus is a wild type OV that replicates only in cells activated by the Ras signaling pathway and specifically targets Ras‐activated cancer cells. Later, as molecular biology techniques advanced, these wild virus strains have been optimized through genetic editing technologies, which leads to the gene-modified OVs. For instance, to increase oncolytic expression in the tumor, an exogenous therapeutic gene is inserted into the OV genome to avoid the occurrence of a systemic immune response and enhance the lethality of the virus. 


    OVs have many features that make them advantageous and distinct from current therapeutic modalities: they replicate in a tumor-selective manner and are non-pathogenic, only minimal systemic toxicity has been detected; their safety features such as drug and immune sensitivity can be built in; and OVs in the tumor increase over time due to in situ virus amplification, whereas pharmacokinetics of conventional drugs decrease. These desirable characteristics of OVs, like specificity for targeted cancer, and exceptional safety against adverse reactions and pathogenic reversion, add to the appeal of oncolytic virotherapy.


    Oncolytic virotherapy is a promising form of cancer gene therapy that employs its agents to find and destroy malignant cells. The specificity, safety, and efficacy of OVs play a significant role in cancer treatment and have become the center of extensive studies to explore their therapeutic potential. Over the past twenty years, genetic engineering has facilitated the rapid expansion of oncolytic viruses, allowing a broad range of potentially pathogenic viruses to be manipulated for safety and targeting. Take the specificity of OVs for an example, there are many methods to improve it such as making use of pathways that are upregulated in tumor cells and not healthy cells and engineering a virus that relies on such a pathway for successful infection thereby rendering the virus incapable of infecting healthy tissue.


    Perhaps the best-studied so far are Herpes viruses of which some strains have been found to have native tumor cell tropism while others have been engineered to improve selectivity. Additionally, various recombinant vaccinia virus strains have shown promise as antineoplastic agents. Other viruses that have been explored as possible vehicles for immunomodulation in cancer include reovirus, Newcastle Disease Virus, Vesicular Stomatitis Virus, and measles. Thanks to oncolytic virus construction technology, this field has been extended to a wide range of engineering scope and many oncolytic programs have moved forward to early-stage clinical evaluation.


    Viruses are at last being harnessed for the benefit of cancer patients. The OV field has moved well beyond proof of principle in human studies, and virus engineering will be the key to its continued advancement in the coming years.