2025 New Treatment Accelerator - Dr. Isabelle Munoz

Despite recent advances in cancer treatments, effective options remain extremely limited in pancreatic cancer, which remains one of the deadliest types of cancer. Therapies that use the body's own immune system to fight cancer (immunotherapy) have transformed the treatment of some cancers, highlighting their potential, but have yet to achieve this impact in pancreatic cancer. This is mainly because pancreatic tumours create a harsh environment that blocks immune cells from entering and prevents them from functioning properly.

In this project, we will develop a new immunotherapy for pancreatic cancer by genetically engineering a patient’s own immune cells to recognise and kill pancreatic cancer cells and to simultaneously overcome the challenges posed by the hostile pancreatic cancer environment.

This treatment involves taking a patient’s own immune cells (T cells) and reprogramming them in the laboratory so they can detect and kill pancreatic cancer cells through the recognition of a mutated protein (known as KRAS) that is present in approximately 40% of pancreatic cancers. To endow the T cells with the ability to overcome the harsh tumour environment, we will use an advanced gene-editing technology called CRISPR that can cut the DNA of the T cell at precise points. These “armoured” T cells will be supercharged with proteins (cytokines or transcription factors) that strengthen immune responses, or which enable the T cells to survive longer and stay active. Importantly, we have already shown that these strategies are effective in animal models of breast, colon, and ovarian cancer, and therefore provide compelling justification for extension into pancreatic cancer.

In this project, we will test these engineered T cells in the laboratory and in animal models of pancreatic cancer. We want to ensure they can shrink tumours and extend survival without causing significant side effects. These preclinical tests are essential to verify the safety and effectiveness of our approach before moving toward clinical trials with human patients.

Our research team has previously performed clinical trials with T cells targeting KRAS in pancreatic cancer patients. Therefore, if we successfully demonstrate that our novel approaches are safe and have improved efficacy as expected, we would be uniquely positioned to explore our therapy in first-in-human trials in pancreatic cancer.

While our initial focus is on pancreatic cancers with a KRAS mutation, our approach is flexible and highly adaptable and in future studies can be modified to target other genetic mutations found in pancreatic cancers. Moreover, because the mutations targeted by our approach are also present in other cancers such as lung and bowel cancers, these therapies have the potential for broad impact.

Ultimately, this research aims to pave the way for a new class of safe, personalised, and highly effective therapy for people with pancreatic cancer and beyond. By developing this innovative therapy, we hope to contribute meaningfully to the Pankind Foundation’s mission to triple pancreatic cancer survival by 2030.