Skin squamous cell carcinoma (cSCC) is the second most common skin cancer. Compared with the more common basal cell carcinoma (BCC), cSCC is difficult to remove with a poor prognosis, and also invades lymph nodes and adjacent important structures. For patients with cSCC, it is very important to introduce a new treatment to improve the poor prognosis. Vaccinia virus has been widely used as a vaccine for human disease prevention, helping humans eliminate variola virus. In recent years, with the discovery of the oncolytic activity of the vaccinia virus, it has once again attracted the attention of scientists as an oncolytic agent, and medical research related to it has begun. Among them, the treatment of SCC is one of the important projects, and it has been proved that the vaccinia virus has a therapeutic effect on various SCC cell lines.
cSCC is a common form of skin cancer that develops in the squamous cells that make up the middle and outer layers of skin. SCC of the skin is aggressive. Although it is usually not life-threatening, untreated skin SCC may grow or spread to other parts of the body, causing serious complications. Most SCC of the skin is caused by prolonged exposure to ultraviolet rays (UV). When the DNA of the flat thin squamous cells in the middle and outer layers of the skin changes (mutates), SCC of the skin occurs. Therefore, cSCC most often occurs on skin exposed to sunlight, such as the scalp, back of the hands, ears, or lips, but can also occur in the mouth, soles of the feet, or on the genitals.
Fig.1 Mechanism of skin cancerization induced by ultraviolet rays. (Alam, 2001)
For the clinical treatment of cSCC, the most critical place is to recognize other risk factors associated with this malignant tumor, including HPV infection, occupational exposure, various genetic skin diseases, scar skin diseases, chronic wounds and burn scars. Most patients with primary SCC have a good prognosis, and treatment is usually simple. However, some of these tumors may relapse or metastasize. Obtaining a complete medical history and performing a systemic skin examination will help identify tumors with a high risk of recurrence or metastasis in addition to tumors that may be easier to treat. For those individuals with metastatic disease, the long-term prognosis should be guaranteed.
Oncolytic virus therapy is a promising cancer treatment that relies on the natural ability of viral infections to replicate and eventually lyse host cells. Various viruses have been shown to exhibit oncolytic properties, including adenovirus, herpes simplex virus, Newcastle disease virus, vesicular stomatitis virus, reovirus and vaccinia. Vaccinia has many advantages as an oncolytic virus, including the ability to infect multiple hosts, effective infection and gene expression, and effective lytic activity.
As a therapeutic agent for cSCC, vaccinia virus has shown lysis of different SCC cell lines in the experiment, showing> 60% cell death within 6 days. Efficient transgene expression and viral replication were observed in the tested tumor cells, indicating the presence of cancer cell factors, which are determinants of the admissibility of vaccinia. Importantly, based on luciferase imaging, there is no evidence that the virus has spread to normal organs or non-tumor sites, demonstrating the replication and activity of tumor-specific viruses. These results indicate that when delivered by intratumoral injection, the vaccinia virus exhibits significant therapeutic efficacy, resulting in dramatic tumor regression without observed toxicity.
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