Chemo- + immunotherapy
A new method of cancer treatment has been created
American scientists have developed a new method for the treatment and prevention of cancer recurrence, based on a combination of chemotherapy and immunotherapy, in which cancer cells removed, damaged and then reintroduced into the tumor serve as triggers for the activation of the immune system. The results of the study are published in the journal Science Signaling (Sriram et al., The injury response to DNA damage in live tumor cells promotes antitumor immunity).
Immunotherapy is a promising strategy for treating cancer by stimulating the body's own immune system to destroy tumor cells. One of its most promising methods — immunotherapy with checkpoint blocking — is based on disabling depleted T cells that can no longer attack the tumor. This method is effective, for example, in the treatment of melanoma, but it is ineffective in many other types of cancer. Therefore, scientists are looking for ways to increase their activity instead of blocking immune T cells.
Researchers from The Massachusetts Institute of Technology found out that if the cells of a removed tumor are treated with chemotherapeutic drugs, and then returned together with the drugs to the tumor, then such damaged cells, no longer posing a danger to the body, are perceived by the immune system as a distress signal that prompts T cells to act.
"When you create cells that have DNA damage, but do not die, under certain conditions, these living damaged cells can send a signal that awakens the immune system," the press release says. According to the head of the study, Professor Michael Yaffe, director of the MIT Center for Precision Oncology Medicine.
This approach is based on a phenomenon known as immunogenic cell death, in which dead or dying tumor cells send signals that attract the attention of the immune system.
In experiments on mice, the authors began with the treatment of cancer cells with several chemotherapeutic drugs in different doses. 24 hours after the treatment, the researchers added dendritic cells to the cups, and after another 24 hours, T cells. To the surprise of scientists, the effectiveness of the drugs was low, and the most effective were low doses of drugs that did not kill the cells completely. When the cause was found out, it turned out that the immune system is stimulated not by dead tumor cells, but by those that were damaged by chemotherapy, but remained alive.
"This is a new concept — immunogenic cell damage, not immunogenic cell death for cancer treatment," explains Jaffe. "When we injected checkpoint blockade inhibitors directly into the tumor along with the cancer cells cured in the cup, the living damaged cells awakened the immune system."
The new method completely eliminated tumors in almost half of the mice. Moreover, when the researchers injected cancer cells into the same mice a few months later, their T cells recognized them and destroyed them before new tumors began to form.
The researchers found that drugs that cause DNA damage to cancer cells are best suited for the new method. Scientists have found that DNA disruption activates stress-responsive cellular pathways that activate T cells, causing them to destroy not only these damaged cells, but also any tumor cells nearby.
The authors hope that the method they have developed will be used to treat a wide variety of cancers.
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