Using an “off-the-shelf” vaccine, researchers from Johns Hopkins Kimmel School of Medicine and Skip Viragh Center for Pancreatic Cancer have demonstrated, for the first time, the ability to generate an immune response targeting mutant KRAS (mKRAS) in people who are at high-risk for developing pancreatic cancer.
What is cancer interception?
Cancer interception is an emerging concept of identifying and treating pre-cancerous cells in people with a high-risk for developing cancer, preventing cancer before it develops. Pancreatic cancer develops from precursor lesions that include pancreatic intraepithelial neoplasms (PanINs) and pancreatic cysts over the span of years. These years represent a unique period for intervention to prevent cancer from developing. Mutant KRAS, the protein responsible for initiating most pancreatic cancer, is often present in pancreatic cysts that have a predisposition to develop into pancreatic cancer making it a potential target for interception.
The Study
In the study, “First-in-human testing of a mutant KRAS vaccine for pancreatic cancer interception in high-risk cohorts” published in Cancer Discovery on July 16th, senior authors Neeha Zaida MD, Elizabeth Jaffee MD, FAACR, and Michael G. Goggins MD, detailed the results from a phase 1 clinical trial demonstrating the vaccine, mKRAS-VAX, was safe and well tolerated and induced mKRAS specific T cells in immunized individuals. This study is the first step to understanding if interception is a safe and effective strategy for preventing pancreatic cancer in high-risk populations.
How the Vaccine Works
Vaccines train the immune system, specifically T cells, to identify cells that express specific proteins and kill them. Cancer vaccines use tumor specific proteins to train T cells to search for and destroy tumor cells. Researchers designed a peptide vaccine, mKRAS-VAX, to target the six most common KRAS mutations found in cancer (G12D, G12V, G12R, G12C, G12A, and G13D).
Trial Design
- 20 participants enrolled, defined as high-risk based on a family history of pancreatic cancer and a pancreatic lesion or cyst
- The mKRAS-VAX vaccine was given 4 times over a 13-week period
- Blood was evaluated at specific time points to measure T cell response to the vaccine
- Additional follow up was available yearly after the vaccine was administered
Results
Of the 20 patients given mKRAS-VAX, 90% had an increase in T cells that specifically recognized mKRAS. Importantly, different types of T cells were increased by mKRAS-VAX, both fast acting effector T cells and long-term memory T cells. These mKRAS specific T cells could be found in patients up to 2 years after their vaccines, suggesting that a durable anti-tumor immune response had been activated.
of patients had an increase in mKRAS-specific T cells
mKRAS-specific T cells remained detectable
median follow-up with no pancreatic cancer diagnoses
Even more encouraging, at a median follow up of 16.5 months, no participant had developed pancreatic cancer. In fact, 37% had a reduction in the size of their pancreatic lesions and five had complete regression of their lesions.
What This Means Going Forward
While this trial provides the first evidence that interception of pancreatic cancer in high-risk patients is possible, it’s important to note that this study was done in a small number of participants with limited long-term follow-up. Evaluation of mKRAS-VAX in a larger population of patients for long-term follow-up is needed to determine the efficacy of this specific strategy for pancreatic cancer prevention. These promising results support more research into interception as a viable avenue for preventing pancreatic cancer in its earliest stages.
The Hirshberg Foundation continues to fund all forms of research into treatment, detection, and prevention so that we can create a future where pancreatic cancer patients live long, healthy lives.
