According tomedia reports, although immunotherapy is a promising potential cancer treatment, but there are still many problems to be solved. Now in a new study at Yale University, researchers have discovered that a cancer uses it to evade “disturbing signals” from the immune system, and, importantly, they have devised a synthetic immune protein that can fight back against it.
The natural version of this immunoprotein, known as leukocyte interleukin-18 (IL-18), is just one of many weapons deployed by the immune system. Specifically, IL-18 can gather T-cells and natural killer cells to fight diseases such as infections and cancer. As a result, the researchers are working on it as a potential cancer treatment, but unfortunately it has not shown real benefits in clinical trials.
To do this, the researchers began to investigate countermeasures that could change the situation, and they did find one. Typically, IL-18 activates immune cells by binding to receptors on the surface of immune cells, but the team found that many types of cancer contain a large amount of expression of leukocyte interleukin-18 binding protein (IL-18BP). It also binds to IL-18 and prevents IL-18 from activating other immune cells. In this case, IL-18BP is like a bait receptor.
With this mechanism in mind, the team studied how to get around it. To do this, they used a process called directional evolution, which mimics natural selection to guide proteins to their desired properties — in which case, those proteins ignore baits and bind only to real receptors. After studying about 300 million IL-18 variants, the researchers found what they wanted.
The team then tested their new version of IL-18 in mice with a range of different tumor types. Sure enough, it slowed the growth of the tumor, and many mice even managed to completely eliminate the cancer cells.
After further examination, the researchers found that synthetic IL-18 increased the number of “stem cell”, which is resistant to cancer for long periods of time. The technique may prove particularly useful for “cold” tumors that do not cause inflammation.
“Since IL-18 can act on cells of the ‘innate’ immune system, such as natural killer cells, it may be effective against ‘cold tumors’ that are resistant to traditional immunotherapy,” said Study co-author Marcus Bosenberg. This is an important unmet requirement and is ready to be addressed by the IL-18 approach. “
The team plans to begin clinical trials of the new synthetic immunoprotein-based drug next year.