A team of oncologists led by experts from the Providence Cancer Institute was able to stop the development of metastases in a patient with pancreatic cancer and reduce those that have already formed. To do this, they replaced the patient’s own T-lymphocytes and forced them to attack the neoplasms. The scientists described the new approach to treatment in an article in the New England Journal of Medicine.
The 71-year-old patient noticed the first symptoms—fatigue, numbness, and bouts of pain—in 2015, and in 2018 the pancreatic tumor had grown to 3.5 cm, clearly visible in the pictures. After a course of chemotherapy, the doctors operated on the woman, then administered a course of radiation and continued chemotherapy all year. However, this did not save it from metastases in the lungs.
Having gone through the sequencing of the metastasis genes, the patient learned that the changes were caused by a particular mutation of the KRAS gene, which encodes the protein of the same name. KRAS mutations are associated with 25% of all cancers, including approximately 95% of pancreatic cancers, 40% of colon cancers, and one-third of lung cancers.
In search of a cure that could save him, the patient met with the authors of the work.
Modification of the patient’s own immune cells is used to fight some types of cancer. In CAR-T therapy, T-lymphocytes needed to recognize and destroy foreign cells are “reprogrammed” using artificial DNA. New proteins appear on the surface of T-lymphocytes that can recognize cancer cells.
However, this approach is currently mainly effective against leukemia and some types of lymphoma. Cells of solid (that is, clear shapes and borders) tumors do not have a receptor that T-lymphocytes can recognize.
The researchers were able to make sure that the patient’s T-lymphocytes recognized the mutant protein inside the tumor cells from the fragments visible on the surface, without affecting the healthy cells.
After one month, the tumors in the lungs were reduced by 67% and were too small for biopsy. After a month, they were reduced by 79%, but in the next nine months their size did not change – perhaps now the formations are made up of dead cells.
“I just passed,” the patient said. “I certainly wasn’t ready to die.”
The authors emphasize that these are just the first steps and there is a lot of research that needs to be done before a similar approach can be used for other patients. They tried to treat another patient in the same way, but he eventually died. It is unclear why the treatment helped the surviving patient. Perhaps the truth is that metastases only affected the lungs – they usually spread over a larger area and affect the liver, which is more difficult to fight.
The scientists plan to invite other patients with incurable cancers to test the method.
“It is too early to draw far-reaching conclusions based on a patient’s data, but if more research in the field of adaptive T-cell therapy shows the same efficacy, it can be assumed that this method may be more effective in the future. It can be used where proven treatments do not help.
It’s also possible that scientists could modify T cells so that they can attack tumor cells better than standard chemotherapy regimens. “Then the method could become a leader in the treatment of pancreatic cancer, such as hematology,” he said.
Suna Isakova, an oncologist at the SberHealth medical online service, told socialbites.ca.
While only one woman responded positively to the treatment of all patients included in the study, she said this study could lead to new advances in the treatment of advanced cancer.
Treatment of pancreatic cancer remains an important and urgent problem worldwide due to many factors: the complexity of early detection, the often aggressive course of the disease, the lack of effective treatment of the late stages, the absence of screening measures for the disease, Isakova notes, the exception is familial forms.
“Pancreatic cancer has no specific symptoms, complaints are similar to those observed in other diseases of the gastrointestinal tract, therefore it is important to consult a doctor in a timely manner. It’s also important to remember that the disease is rare and oftentimes symptoms are caused by noncancerous diseases. Endosonography (endoscopic ultrasound) and MRI of the pancreas are used as effective diagnostic methods,” he says.
In recent years, there has been no significant change in the treatment of pancreatic cancer in the world, for this the same methods are used as in other types of cancer – surgical treatment, chemotherapy before and after surgery. Perhaps more research in the field of cancer immunotherapy will help fight pancreatic cancer more effectively.