In 2018, two pioneers in cancer immunotherapy won the Nobel Prize in Physiology or Medicine. This newly pioneered field has completely changed the treatment of cancer, and many cancer patients have changed from “no medicine to cure” to “10 years of cancer free”.
The top academic journal《Cell》published a new paper on cancer immunotherapy. The positive data shown in the research shows that this field that has been recognized by the Nobel Prize is expected to be further expanded.
The mechanism of cancer immunotherapy is easy to understand: our immune system can recognize viruses, bacteria and other pathogens, attack them, and keep us healthy. As long as the immune system learns to recognize cancer cells, they can be eliminated as foreign pathogens.
What immune cells are best suited to perform this function? The researchers focused their attention on a common type of white blood cell called polymorphonuclear neutrophils. This cell has a characteristic, the immune system can control its location.
As a member of the innate immune system, neutrophils can fight many different pathogens. Can they also exert the same killing effect on cancer cells?
In this research, scientists at the University of Chicago made a breakthrough. They found that human neutrophils can release an elastase called ELANE, and this enzyme can specifically activate the apoptosis pathway of cancer cells to produce anti-cancer effects.
“Cells are constantly changing and mutations are constantly accumulating. Some people will get cancer, others will not,” said Professor Lev Becker, the leader of this study. “The pathway we discovered may be the original mechanism by which the immune system eliminates these mutant cells. .”
How is this magical effect achieved? The researchers also answered in the paper. As an elastase, ELANE can degrade some proteins, including the CD95 (Fas) protein involved in apoptosis.
After CD95 is degraded, a protein fragment called the “death domain” is released, which plays an important role in the process of apoptosis. Interestingly, histone H1 bound by this death domain happens to have a high level of expression in cancer cells. Originally, cancer cells used histone H1 to stabilize their genome. Unexpectedly, they exposed their weaknesses, allowing scientists to find them.
It is precise because the levels of histone H1 expressed by cancer cells and ordinary cells are different, scientists have found that ELANE can effectively kill a variety of different cancer cells without accidentally injuring the surrounding healthy cells. What’s more noteworthy is that the researchers found that ELANE has a killing effect on refractory cancers such as triple-negative breast cancer, melanoma, and lung cancer, indicating that it may become an “unrestricted cancer type” innovative treatment.
Further analysis found that another elastase PPE similar to ELANE is expected to bring a stronger therapeutic response. The researchers also said they would explore how to maximize the efficacy of the two proteases for cancer treatment in the future.
Recently, a company called Onchiles Pharma announced the completion of a US$7 million financing to promote the development of this therapy. The research leader, Professor Becker, is one of the company’s founding scientists. We also look forward to this innovative treatment being validated as soon as possible to benefit cancer patients worldwide.
Reference
[1] Chang Cui et al., (2021), Neutrophil elastase selectively kills cancer cells and attenuates tumorigenesis, Cell, DOI:https://doi.org/10.1016/j.cell.2021.04.016
[2] Anthony Letai, (2021), Death in the Fas, ELANE, Cell, DOI:https://doi.org/10.1016/j.cell.2021.05.02