A new strategy against pancreatic cancer

Pancreatic tumor is one of the most dangerous and fatal tumors ever. A team from the LMU clinic in Munich has found a way to effectively combat this cancer, at least in the lab.

Immunotherapy is traded as hot iron in the fire

Pancreatic tumors are among the most dangerous and lethal – and therefore are particularly intensively researched. Now a team led by Professor Sebastian Kobold from the Department of Clinical Pharmacology at the LMU Klinikum in Munich has found a way to combat this cancer effectively, at least in the lab. The researchers’ findings were published in the journal Nature Biomedical Engineering.

Anyone who develops a tumor in the pancreas still has a small chance. Five years after diagnosis, only ten percent of patients are still alive, despite best medical practice. Not discouraged, researchers continue to search for new treatments that can improve the predicament. “Immunotherapy is treated like hot iron in the fire, and we know from preclinical work that T cells in the immune system can be very effective in fighting tumors,” says Sebastian Kobold.

With emphasis on the word “can”. Because in order for these defensive cells to be effective, they must first reach the area of ​​the tumor and be able to penetrate the actual cancer cells. This is exactly where the problem lies. On the other hand, pancreatic cancer cells are surrounded by stroma tissue that is difficult to penetrate. On the other hand, cancer cells send a messenger substance called CXCL16. CXCL16 attracts a group of immune cells that prevents the tumor from attacking rather than releasing it. Unfortunately, the population of T cells that could theoretically fight a tumor lacks the receptors that can respond to CXCL16 signaling with an attack.

if you don’t

Better to use genetic engineering to modify T cells so that they produce the missing receptor. That’s exactly what the team of researchers led by Kobold did. So-called CAR-T cells were used for this. CAR-T stands for “chimeric antigen receptor T cells”. The name describes the genetic modifications that turn T cells into tumor killers. For immune cells to recognize cancer cells, scientists use genetic engineering to create a type of antenna on the surface of T cells, which recognizes a very special molecule on the surface of cancer cells according to the lock-and-key principle. . With the help of the antenna, the boosted T cells track down the enemies, stick to them, and eventually destroy them.

In order to specifically target pancreatic tumor cells, the Munich researchers also built the missing receptor gene in CAR T cells. With a resounding effect: “In all laboratory tests, CAR-T cells processed in this way found their target and attacked the tumor cells of the pancreatic tumors,” Kobold says. pancreas”.

Motivated by their findings, the researchers began preparing for extended clinical trials. First of all, it is about the production of adapted CAR-T cells in a way that meets all the requirements of the authorities. Preparations for clinical studies, which are indispensable for use on humans, also act at the same time. “In a few years, we will then know if our hopes for a new treatment for pancreatic tumors will come true,” the doctor explains.

those:
T cells armed with CXC chemoreceptor type 6 promote adoptive cell therapy for pancreatic tumors. The Nature of Biomedical Engineering (2021).