Researchers investigated a two-pronged immunotherapy approach that eliminates metastatic breast cancer in mice. The corresponding study was published in Cancer Discovery.
The 5-year survival rate for women with metastatic breast cancer in the US 30%. The same figure stands at 19% for men. In around 70% of patients with metastatic breast cancer, tumors have spread to their bones. Until now, the condition has responded poorly to immunotherapy.
In the current study, researchers found that blocking a molecule called p38MAPK sensitizes the tumor microenvironment to attacks by the immune system. However, while p38MAPK inhibitors alone reduced tumor size, they didn't eliminate tumors entirely. The researchers thus added another therapy- an OX40 agonist which binds to and activates T cells- to the p38MAPK inhibitor. In doing so, they were able to destroy tumor cells that had spread to bones while protecting against bone loss.
In experiments with mouse models of human metastatic breast cancer that had spread to bones, the researchers found that mice that received both treatments were alive and tumor-free for at least 80 days after treatment. By comparison, only around half of those taking one of the two treatments alone were alive 60 days after treatment.
"If we targeted the microenvironment to make it more sensitive to T cells and simultaneously hit the gas on the T cells, all of the mice were cleared of the metastatic tumors," said senior author Sheila A. Stewart, PhD, the Gerty Cori Professor of Cell Biology & Physiology at Washington University School of Medicine in St. Louis in a press release.
"If we came back after two weeks and challenged the mice again with the same tumor cells, their immune systems could clear those cells as well. It appears that their immune systems developed long-term memory and knew to attack those returning cancer cells. The mice look like they're basically vaccinated against the cancer."
Already, three different OX40 agonists are undergoing phase 2 clinical trials for cancer, including breast cancer. Meanwhile, p38MAPK inhibitors have been investigated for various conditions, including rheumatoid arthritis and obstructive pulmonary disease. The researchers hope that their research will interest companies that make both drugs to partner with them to develop a clinical trial for metastatic breast cancer.
Sources: Science Daily, Cancer Discovery
