Oncolytic viruses (OVs) are a new force in immunotherapy, a therapeutic strategy that has attracted a lot of attention and made great progress in recent decades. As researchers explore further on oncolytic viral therapies, more and more types of viral vectors have been developed to obtain the best therapeutic effect.
Currently, there are three oncolytic viral drugs successfully marketed. In 2003 and 2005, the CFDA (China Food and Drug Administration) approved the marketing of Gendicine and Oncorine respectively. However, these two drugs have not received international recognition due to the combination of imperfect clinical trial standards and lenient approval policies in China. The first to be recognized by the industry was herpes simplex virus T-Vec (Imlygic), which was approved by the FDA in 2015 for the treatment of advanced melanoma and subsequently approved for marketing in Europe and Canada in 2016.
The United States is one of the leading countries for OV research. As of August 2020, there were 66 clinical studies of OVs in the United States in the clinicaltrials.gov database. Of these, herpes virus, cowpox virus, and adenovirus are the top three types, and others include measles virus, eutherian virus, coxsackievirus, Maraba virus, Seneca Valley virus, and poliovirus. These viruses are arguably the most popular research areas at present.
Obviously, the most critical step in the development of OVs is the selection of viral strains, and the advantages of these viruses make them a popular direction for research and development.
Herpesvirus (HSV) is an enveloped, double-stranded DNA virus. Its genome is large and suitable for larger gene fragment insertion; at the same time, it is more replicative and better able to kill tumor cells. It is easy to design and can co-express non-viral genes to enhance therapeutic effects, and also is outstanding for not triggering inflammation and immune response.
Vaccinia Virus (VV) is a double-stranded DNA virus with a large genome about 190 kbp long. Unlike other viruses, VV has two forms, IMV (intracellular mature virus) and EEV (extracellular enveloped virus). The advantages of this virus are that it replicates rapidly. What's more, the genome is not integrated into the host cell chromosome and thus does not cause insertional mutagenicity. The genome is also large enough to insert large segments of exogenous genes.
Adenovirus (Ad) is an envelope-free, double-stranded DNA virus. Oncolytic adenoviruses are known as conditionally replicating adenoviruses (CRADs), which have many advantages, such as a wide range of infected cells (almost all types of cells can be infected), insertional mutagenicity-free, high virus titer, etc. However, adenovirus also has some disadvantages, such as strong autoimmunogenicity, which may cause immune rejection of adenovirus by the body itself; in addition, some studies have shown that adenovirus can be easily enriched in the liver by intravenous injection, causing toxic side effects.
As immunotherapy is emerging for tumors, a large number of clinical studies have confirmed that it has a high level of clinical safety, and its infection of tumor cells enhances the body's anti-tumor immune response, and can produce a more durable response. In the future, research on lysing viruses may enable a new chapter in cancer treatment.