In the clinical trial of oncolytic vesicular stomatitis virus expressing interferon-β (VSV-IFN-β), a large group of patients initially achieved a preliminary response, but then the disease relapsed. A few days ago, in a study entitled “Oncolytic virotherapy induced CSDE1 neo-antigenesis restricts VSV replication but can be targeted by immunotherapy” published in the international journal Nature Communications, scientists from Mayo Clinic and other institutions found that a cancer vaccine may be an effective way to prevent cancer evolution and tolerance to therapy.
Those researchers investigated a virus that kills cancer cells in clinical trials. They added that, as observed in mice, at first some patients responded to the treatment, but then the tumor quickly developed resistance. The researchers said that using a vaccine may be able to predict and use specific mutations that promote the tolerance of tumor cells to viral therapy, and when the vaccine is assessed in mice models, it may induce the body’s immune system to destroy tumor cells that are resistant to therapy. The results may also be applicable to other types of treatments that drive drug tolerance, such as targeted drugs for PARP inhibitors.
In this study, researchers showed for the first time that this type of vaccine may be used to overcome the evolution and tolerance of cancer. It is well known that treating tumor cells with anticancer viruses may induce mutation and promote cancer cells to evolve, thus escaping viral attacks and making viral therapy ineffective. Scientists found that tumor cells have a predictable mutation after being infected with the virus. Viral therapy causes mutations in a gene called CDSE1 in cancer cells, which protects cancer cells from viruses by slowing down their replication.
The mutated CDSE1 protein produced by the CDSE1 gene produces a unique antigen (a structure recognized by the immune system as a target), helping researchers develop new vaccines. Researchers have developed a new vaccine that targets the mutation and found that injecting the vaccine into mice treated with the virus may induce the immune system to destroy tumor cells that are resistant to drugs, and kill cancerous cells, thereby reducing the tumor size.
Researchers take advantage of the tumor’s defense mechanism by vaccinating mutant cells, known as “traps and ambushes”, which drive tumors to evolve in a special way and act as a defensive mechanism against treatment. This vaccine induces the host’s immune system to destroy tumor cells that are resistant to drugs, thereby preventing the further development of cancer. In this study, the researchers aim to understand the mechanism of immunotherapy, who used viruses for initial treatment to promote tumor cells to change in a predictable way, and then took advantage of the vaccine to precisely target mutations to prevent further cancer development.
This principle may be widely applicable, because drug tolerance of is a big problem for many types of therapies. Researchers are currently exploring the possibility that this method can be applied to other treatments, such as tumor mutation and evolution. In summary, the results of this study suggest that the combination of first-line drugs with escape-targeted immunotherapy may be suitable for a variety of therapies that drive tumor mutation/evolution. At the same time, it can produce new targeted immune peptide groups related to acquired drug tolerance.