A team at Providence Cancer Institute, led by renowned oncologists, achieved a breakthrough in pancreatic cancer by halting the spread of metastases and shrinking existing tumors. Their treatment involved taking the patient’s own T-lymphocytes, engineering them to target cancer cells, and then reintroducing them into the body. The study detailing this approach appeared in the New England Journal of Medicine.
The 71-year-old patient first reported fatigue, numbness, and intermittent pain in 2015. By 2018, imaging showed a pancreatic tumor measuring 3.5 cm. After initial chemotherapy, surgeons removed the tumor, followed by radiation and a year-long course of further chemotherapy. Despite these efforts, metastases formed in the lungs.
Genetic analysis of the metastatic lesions revealed a mutation in the KRAS gene, which drives the production of a key protein associated with many cancers. KRAS mutations are present in about a quarter of all cancers and occur in roughly 95% of pancreatic cancers, 40% of colorectal cancers, and about one-third of lung cancers.
Seeking a potential cure, the patient connected with the researchers who authored the work.
Adoptive cell therapy, where a patient’s immune cells are modified to better recognize and attack cancer, is a growing field. In CAR-T therapy, T-lymphocytes are reprogrammed using synthetic DNA to display new proteins that recognize cancer cells. This approach has shown success against certain leukemias and some lymphomas, but solid tumors have posed challenges because their cells often lack the receptors needed for T-cell recognition.
In this study, scientists trained the patient’s T cells to recognize a mutant protein inside tumor cells, using fragments detected on the cell surface as a guide. The result was selective targeting of cancer cells while sparing healthy tissue.
Within a month, lung tumors shrank by 67% and became too small to biopsy. After another month, reductions reached 79%, and over the following nine months there was no further size change—likely indicating that the remaining masses consisted of dead cancer cells.
“I just passed,” the patient recalled, noting that life was not ready to end.
The researchers caution that this represents early progress and that more work is needed before this method can be used broadly. A second patient treated with the same strategy did not survive. The reasons behind the different outcomes remain unclear, and it is possible that lung metastases respond differently than cancer in other organs such as the liver.
Plans call for inviting additional patients with cancers deemed incurable to participate in further trials.
Lead scientists stressed that drawing broad conclusions from a single patient is premature. If similar responses are observed in larger studies, adaptive T-cell therapy could become a viable option when standard treatments fail. There is optimism that future refinements could make T-cell therapy competitive with conventional therapies in pancreatic cancer.
Experts involved in the study noted the potential for expanding this approach to other cancer types as research continues to unfold.
Isakova, a clinician with a digital health service, commented on the findings, acknowledging that while this study shows promise, broader validation is essential. She emphasized the importance of early evaluation for pancreatic cancer, given its subtle onset and the urgent need for more effective treatments. Endoscopic ultrasound and MRI remain important tools for diagnosing pancreatic conditions.
Overall, the field of pancreatic cancer treatment continues to rely on a combination of surgery, chemotherapy, and radiation, with immunotherapy representing a hopeful frontier. Ongoing trials aim to determine how best to apply immune-based approaches alongside existing therapies to improve outcomes for patients facing this challenging disease.