Harnessing the immune system to fight cancer is a constantly evolving field of medicine, but the most stubborn and least responsive to immunotherapy is metastatic breast cancer.
Scientists have now found a way to treat the area around breast cancer tumors that have metastasized to the bone, making these secondary tumors vulnerable to attack by the immune system.
Common immunotherapies (immune checkpoint inhibitors) boost the activity of T cells to attack cancer. But researchers at the Washington University School of Medicine (WUSTL) in St. Louis used his two-step approach instead to boost cancer-fighting immune system cells.
“Once breast cancer spreads to other parts of the body, it becomes very difficult to treat. Sheila A. Stewart said. “About 70% of patients with metastatic breast cancer have tumors that have spread to the bone.
“Our study suggests that two therapeutic modalities could potentially be used: one to sensitize the microenvironment of myeloid tumors to immunotherapy; The first is to activate T cells that target these bone metastases in a way that eliminates tumors, prevents cancer recurrence, and protects against bone loss in the process. ”
In studies in mice, the team found that blocking the p38MAPK molecule reprograms tumor regions to become more vulnerable to attack by immune cells (T cells and macrophages) and signaling molecules called anti-tumor cytokines. I discovered that Shrinking tumors were then removed using OX40 agonist therapy, which binds and activates T cells.
By enhancing the activity of T cells and macrophages, a dream team was born to fight cancer. It also enables long-term immune memory because macrophages continue to present recognizable fragments of dead tumor cells, called cancer antigens, to T cells, ensuring that T cells quickly attack and kill new growths. became.
Encouragingly, all mice receiving dual therapy were alive and tumor-free 80 days after treatment. was 50%.
“By targeting the microenvironment to increase sensitivity to T cells and simultaneously gassing them, all mice cleared metastatic tumors,” Stewart said. “If they come back two weeks later and attack the mice again with the same tumor cells, the mice’s immune system is able to eliminate those cells as well. It seems to have known to attack cells. Mice basically look like they’ve been vaccinated against cancer.”
Three OX40 agonists currently in phase II clinical trials for the treatment of cancer, including breast cancer. Scientists are investigating his p38MAPK inhibitor in trials for rheumatoid arthritis and chronic obstructive pulmonary disease.
“We hope our research will be of interest to the companies that manufacture these drugs so they can work on developing clinical trials that can investigate this strategy in patients,” Stewart said.
The study was published in a journal cancer detection.
Source: Washington University School of Medicine in St. Louis
