Rotavirus vaccines against cancer
Weakened rotaviruses will join the fight against oncopathology
Yulia Vorobyova, Vesti
Today, numerous vaccines protect people from many infectious diseases. But what happens if you direct this powerful weapon to destroy another, even more dangerous target?
In a breakthrough study published in the journal Science Translational Medicine (Shekarian et al., Repurposing rotavirus vaccines for intratumoral immunotherapy can overcome resistance to immune checkpoint blockade), an international team of scientists suggests using rotavirus vaccines in oncology. To be more precise, the idea of specialists is to use these drugs to overcome resistance to cancer immunotherapy.
The team focused on the resistance that the body often provides to immunotherapeutic treatment called checkpoint inhibitor therapy.
Let's explain that some cancer cells have a protein called PD-L1. And the key soldiers of the immune system's army, T cells, have a protein known as PD1 on their surface.
PD-L1 is the PD1 ligand. When, with the help of the latter, the T-cell binds to the PD-L1 protein of a healthy cell, it understands that it does not need to be attacked.
Meanwhile, insidious malignant cells with PD-L1 protein can use it to elude vigilant T cells, posing as healthy ones. Subsequently, they multiply and spread.
Checkpoint inhibitors, in turn, do not allow such "infiltrators" to get through the "checkpoint".
Such drugs are used to treat many types of oncopathology, for example, Hodgkin's lymphoma, lung, bladder, ovarian and kidney cancers.
However, the problem is that cancer cells can develop resistance to such therapy. In this case, T-cells cannot restrain the growth of deadly tumors.
And here comes the finest hour of rotavirus vaccines.
The researchers found that these drugs (by the way, have already proven their safety and approved for use) increase the effectiveness of treatment with checkpoint inhibitors and can be used as anti-cancer agents.
"We found that rotavirus vaccines have both immunostimulating and oncolytic properties. In addition, they can directly kill cancer cells. Intra–tumor rotavirus therapy has an antitumor effect, which is mainly immune-mediated," Tala Shekarian, the first author of the study, an employee of the Cancer Research Center in Lyon and the University Clinic of Basel, told the Medical Xpress portal in an interview.
She clarified that the team has already attributed RotaTec and Rotarix to the number of rotavirus vaccines with such properties.
At the moment, studies have been conducted on cell lines and animal models, and the results have pleasantly surprised scientists.
In particular, rotavirus vaccines activated the transcription factor NF-kB in human cells. This enhanced protection against model cancer resistant to checkpoint inhibitors.
Additional studies have shown that rotavirus vaccines also activate the intracellular RIG-I receptor. This stimulates the immune response, and the protective cells come to the aid of the body.
"In some mouse tumor models, the intra–tumor rotavirus vaccine helped to cope with resistance to immunotherapy and enhanced the effect of treatment aimed at control points," Shekaryan added.
This study will undoubtedly become an important milestone in the history of the creation of highly effective anti-cancer therapy. After all, it assumes that not only rotaviruses, but also other viruses (weakened during the creation of vaccines) also have powerful antitumor properties.
The team also believes that the oncolytic properties of well-studied viruses can be used to create antitumor immunity in humans.
According to experts, in order to increase the efficiency of future work in this area, it is necessary to rely primarily on already proven and commercially available drugs.
"Rotavirus vaccines are a product for children and adults intended for clinical use. Therefore, it will be possible to quickly introduce immunization strategies using an intra–tumor weakened rotavirus into clinical practice," Dr. Shekaryan concludes.
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