MIT and Dana-Farber researchers identify a hidden vulnerability.
Pancreatic cancer remains one of the most lethal and challenging cancers to treat, with a 5-year survival rate of just around 10%. Immunotherapies, like checkpoint inhibitors, have brought hope to many cancer types, but have shown limited success in pancreatic cancer.
Now, researchers from MIT and Dana-Farber Cancer Institute have uncovered a potential new path forward: cryptic peptides.
These are fragments of proteins derived from genomic regions previously thought to be “non-coding” – effectively hidden from traditional cancer target discovery methods.
In their latest study, the team identified over 1,700 cryptic peptides in pancreatic tumor samples, with about 500 found exclusively on pancreatic cancer cells, not in healthy tissue.
Using these cryptic peptides, they engineered T cells capable of recognizing and attacking pancreatic cancer cells in lab-grown organoids and mouse models. The results? Tumor growth was significantly slowed, marking the first demonstration of T cells targeting cryptic peptides in pancreatic cancer.
Beyond T cell therapies, the research also opens doors to cancer vaccines and T cell engagers that could harness these hidden targets.
Although clinical application is still a few years away, this discovery represents an unexpected vulnerability in pancreatic tumors — and could reshape how we think about immunotherapy for one of the deadliest cancers.
It’s a powerful reminder that even in the most challenging cancers, new targets can be found if we look in the places we least expect.
