THE immunotherapy drugs they are delivering important results in the fight against cancer, but they are so strong that they can be toxic to the rest of the human body. The idea behind immunotherapy drugs is simple: Doctors inject special types of drugs into the patient, especially proteins such as antibodies and cytokines prepared or modified in the laboratory, thus activating the immune cells of the person involved (T cells, NK cells, etc.) and helping these cells to fight the tumor . Basically, immunotherapy drugs work as a powerful cocktail that strengthens the patient’s immune system.
“After being prescribed by a doctor, immunotherapy drugs are administered intravenously”, he claims Li Tang, head of the Laboratory of Biomaterials for Immunoengineering at the EPFL School of Engineering. “Once inside the body, the therapy spreads everywhere, not just where the tumor is or any metastases. The problem is that the proteins in drugs are so strong that they damage healthy tissue“.
Many of the immunotherapy treatments already available have been shown to be highly effective against cancer in studies preclinical, but often they cannot be used to save people because they are too toxic to the rest of the body. “The treatments that are used in patients today have been toned down, so they are less potent“Says Tang. “This makes them safer, but also less effective in destroying tumors. Our goal is to maintain the full power of immunotherapy ”.
Tang and his team then developed a method whereby immunotherapy proteins are activated only when they enter tumor tissues. The EPFL team is one of the pioneers in developing this type of technology through a universal chemical approach. “We have been able to achieve this thanks to our interdisciplinary approachTang said. “Our method is based on techniques of both chemistry and immune engineering.”
There Research was published in the scientific journal Science Advances.
New immunotherapists: this is what the research says
Yu Zhao, a researcher at Tang’s lab, began by using the chemical properties around tumors. “The tumor microenvironment is different from the rest of the body. The pH is lower, which means it is more acidic and has a high reducing potential“Said Zhao who used this information, already known to scientists, to develop a kind of polymer shield for protein drugs that would let them travel harmlessly through the body until they reach the tumor.
“To create a shield, I first developed stimulus-sensitive chemical bonds that attach to the surface of protein molecules, like tiny hooks.“Explained Zhao. “Then I took some polymers, which are long chains of molecules, and I “hooked” them to the bonds of the protein molecules. Once attached to the surface of the protein, the polymers envelop them, like a protective shield ”.
That shield is designed to rupture when exposed to the unique chemical environment in the tumor tissue. Tang explains: “Chemical reactions in the tumor microenvironment break the bonds on the surface of the protein, thereby removing the polymer shield. The protein drugs are then free to selectively activate the patient’s cancer-fighting lymphocytes in the tumor tissue. “
It took Zhao several years of research and countless experiments to find the right chemical combination for the new method. And it will likely take several more years, along with a significant amount of funds, before the method is potentially used clinically to cure cancer.
New immunotherapists: stem T cells could help me immunotherapy in cancer treatment
In a search for the Yale Cancer Center, scientists have shown that stem T cells within some lymph nodes may be natural cancer fighters. Targeting these T cells, which are a type of white blood cell, with immunotherapy drugs could increase the number of cancer patients who respond to treatment.
The results of the study have been reported in the scientific journal Science Immunology.
“Therapies that use the immune system to destroy cancer have been a game changer for patients with lung and other cancers“, he has declared Nikhil Joshi, Ph.D., Assistant Professor of Immunobiology, member of the Center of Immuno-Oncology at Yale Cancer Center and senior author of the study. “But not all people respond to immunotherapy drugs, so it was important for us to discover the role of these special T cells in tumor growth. “
During the research, the scientists first developed a new animal model in which they could observe stem T cells in tumors over the course of several months of tumor growth and determine how stem T cells survive.The researchers found that stem T cells do not persist in the tumor for very long, which means they are replenished from somewhere else in the body.
Nearby lymph nodes, an immune organ containing many of these stem T cells, were replenishing the supply. Occasionally, some stem T cells leave the lymph node and travel to the tumor. This keeps the tumor supplied with new cancer-fighting T cells. Researchers believe this is important for slowing cancer growth. An analysis of immune cells isolated from lung cancer patients confirmed that stem T cells are found in the lymph nodes near the lung.
“T cells in tumors are depleted, but the results of our study show that stem T cells within nearby lymph nodes are not depleted during the course of the disease”, he has declared Kelli A. Connolly, researcher at the Yale Cancer Center and lead author of the study. “This could be an important therapeutic advance as the ability to respond to immunotherapy is preserved“.
“We are focused on developing therapies that will activate stem T cells in the nearby lymph node and lead them in the fight against cancer.“Concludes Joshi. “We plan to continue this work and focus on how to improve these therapeutic responses to help patients. “