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Steve Jobs, the scientific genius who changed the world, died of complications of pancreatic cancer. In recent years, the number of people suffering from pancreatic cancer has been increasing, and 90% of cancer patients may die within one year after diagnosis. The nickname "the king of cancer" has also become a hot spot in medical research.

CRT-T therapy is very effective in the treatment of leukemia, but it has hit a wall in the treatment of pancreatic cancer.

CAR-T therapy is very effective in the treatment of malignant hematological tumors (also known as leukemia). Therefore, both medical and scientific circles hope that CAR-T therapy can be used to treat solid tumors, especially pancreatic cancer.

The principle of CAR-T therapy is to extract T cells responsible for immune response from patients, then add antibodies that can recognize cancer cells, and activate T cells through genetic engineering to make "CAR-T cells". After a lot of culture, it is injected back into the patient's body, so that immune cells can accurately identify and attack tumor cells.

However, when CAR-T was used to treat pancreatic cancer, it encountered two iron walls. 1 means that pancreatic cancer has a special tumor microenvironment (TME), which keeps T cells out of the door and makes CAR-T unresponsive. The second obstacle is that if the CAR-T mark also exists on normal cells, normal cells will be attacked, resulting in a situation of "no distinction between the enemy and ourselves".

Australian scientists helped CAR-T install a unique "switch" to defeat the king of cancer! ?

Medical researchers at the University of New South Wales in Australia have developed an improved CAR-T therapy, which can improve the cure rate of pancreatic cancer and solve the phenomenon that CAR-T therapy attacks normal cells in the body. The study was published in the international magazine Gut.

Help CAR-T install unique switch Fab antibodies? Accurately identify pancreatic cancer

There are Fab fragments in pancreatic cancer cells, which only exist in pancreatic cancer cells and not in other normal cells, so they are very suitable as recognition targets. Using this feature, scientists first induced a specific antibody fragment from Fab fragment, and then added the specific Fab antibody fragment to CAR-T to form a unique switch.

When CAR-T with Fab antibody switch comes into contact with Fab fragments on the surface of pancreatic cancer cells, it will attract and combine with each other, making CAR-T in an open state, breaking through the special tumor microenvironment barrier of pancreatic cancer, and accurately identifying pancreatic cancer, thus solving the problem that T cells can not distinguish between friend and foe and injure normal cells by mistake.

CAR-T therapy can effectively activate T cells and completely eliminate tumors under the action of accurately identifying cancer cells. Moreover, these CAR-T cells with Fab antibody switches have a short half-life, that is, they will fail after being used to treat tumors, so they will not have toxic and other adverse effects on normal tissues.

In animal experiments, the tumor of pancreatic cancer mice completely disappeared without any side effects.

Scientists used experimental mice with pancreatic cancer to carry out animal experiments, and found that CAR-T therapy with Fab antibody switch completely eliminated pancreatic tumor cells, and the speed of cancer treatment could be controlled by adjusting the switch. More importantly, it has no cytotoxicity or side effects on experimental mice. So all parties are paying attention to this clinical trial, hoping to see the day when patients with pancreatic cancer fully recover.

Paper document: Gut is the official magazine of British Gastroenterology Society. The academic influence factor in recent years is 17.438+06. The content focuses on the fields of gastroenterology and hepatology, and enjoys a high reputation in publishing first-class clinical research on digestive tract, liver, bile duct tree and pancreas. Provide the latest, authoritative and clinical-oriented reports in all fields of gastroenterology and hepatology. Routine functions include articles describing new disease mechanisms and new management strategies, including diagnosis and treatment strategies, which may affect clinical practice in the foreseeable future.