An experimental form of immunotherapy caused a 72% reduction in the tumour size of a woman with pancreatic cancer.
In a study published in the New England Journal of Medicine, researchers in Oregon outlined the case report of a 71-year-old with pancreatic cancer. The patient, Kathy Wilkes, had received a diagnosis of adenocarcinoma of the head of the pancreas at 67 years of age. Prior to her diagnosis, the woman suffered from recurrent episodes of pancreatitis and biliary stricture. In 2018, she underwent eight rounds of chemotherapy, radiation, and a Whipple procedure (removal of part of the pancreas). She remained cancer-free until 2019, but soon after developed lung metastasis. Her specialists suggested further chemotherapy rounds as her only solution. But Kathy decided to conduct her own research.
I knew that regular chemotherapy would not save my life and I was going for the save.
Kathy Wilkes
Her search led her to a 2016 case report which detailed the use of experimental gene therapy for treating a patient with advanced colon cancer. The gene therapy targeted a specific mutation, KRAS G12D, which is found in solid tumours. Kathy then reached out to Eric Tran, the study’s author. Although Kathy and the case report patient had different tumours, they both had the same genetic mutation. Thus, making her compatible with the experimental treatment.
This particular mutation is common in tumours that arise from epithelial cells, such as lung, ovarian and pancreatic cancers. We for the first time have an approach that could allow the treatment of a large variety of tumours beyond the small number of tumours that CAR-T cells can be used in a very specific type of immunotherapy.
Eric Rubin, the New England Journal of Medicine’s editor-in-chief
5-Year Survival Rate of Less Than 8%
In 2020, an estimated 495,773 pancreatic cancer cases occurred worldwide, while approximately 466,00 deaths were reported from the cancer. According to the American Cancer Society (ACS), an estimated 49,000 people are expected to die from pancreatic cancer in 2022. Moreover, it accounts for 7% of all cancer deaths in the country.
The pancreas is an organ located behind the lower part of the stomach. It is responsible for releasing enzymes and various hormones such as insulin. Both cancerous and non-cancerous tumours can develop in the pancreas. Although pancreatic cancer can develop in any part of the pancreas, the most common type begins in the cells lining the ducts. This type of cancer is called pancreatic ductal adenocarcinoma.
Common signs and symptoms of pancreatic cancer include abdominal pain that radiates to the back, jaundice, unintended weight loss, light-coloured stools, and dark urine. Moreover, diabetes, blood clots, and swelling of the gallbladder or liver may occur. However, the symptoms of pancreatic cancer can also resemble other diseases and often do not appear until an advanced stage of cancer. Furthermore, there are currently no specific screening tests for the detection of early-stage pancreatic cancer in those without symptoms. As a result, 80% of pancreatic cancer cases present at an incurable stage where the tumour is past the point of resection.
Pancreatic ductal adenocarcinoma is one of the most lethal cancers and is resistant to current immunotherapies. It accounts for 90% of all pancreatic cancers and has a 5-year survival rate of less than 8%.
Recently, researchers have begun exploring immunotherapies for the treatment of aggressive cancers. CAR-T therapy has successfully improved patient outcomes in various aggressive blood cancers. However, since it’s not as effective against solid tumours, the team in Oregon explored a different type of immunotherapy.
72% Reduction in Pancreatic Tumor
At Oregon’s Providence Cancer Institute, Eric Tan and his team worked on a new approach for Kathy’s tumour. Called T cell receptor, or TCR, therapy, the approach involves genetically engineering the patient’s T cells so they can identify mutant antigens within cancer cells.
We’re talking about the chance to distinguish tumour cells from non-tumour cells in a way that we never could before.
Eric Rubin, the New England Journal of Medicine’s editor-in-chief
Kathy received an infusion of these T-cells and within a month researchers noted a 62 per cent reduction in her lung tumours. And six months later, her tumour shrunk by 72%. Although Kathy isn’t cured of her cancer, the researchers have not found any sign of cancer growth since her treatment. Thus, her cancer remains stable.
According to researchers Eric Tran, the team has also tried the experimental treatment in one other pancreatic cancer patient. However, it failed to cause a similar outcome and the patient died 6 months later. It is unclear as to why the treatment worked in Kathy but not the other patient.
Nevertheless, this very promising research can potentially open doors for this type of immunotherapy. And help provide a solution to those suffering from advanced solid tumours.
Reference:
Rom Leidner et al, Neoantigen T-Cell Receptor Gene Therapy in Pancreatic Cancer, New England Journal of Medicine (2022). DOI: 10.1056/NEJMoa2119662
