Pancreatic cancer vaccine boosts immune response in high-risk patients
Pancreatic cancer vaccine boosts immune response in high-risk patients
Pancreatic Cancer Vaccine Boosts Immune Response in High-Risk Patients
A vaccine targeting common KRAS mutations has been shown to be safe and stimulate KRAS-specific T-cell responses in 90% of study participants who are at high risk of developing pancreatic ductal adenocarcinoma (PDAC), according to phase I clinical trial results. The study, published in Cancer Discovery, a journal of the American Association for Cancer Research (AACR), provides new hope for the prevention of pancreatic cancer, one of the most lethal forms of cancer.
Pancreatic cancer is often diagnosed at advanced stages and carries a low five-year survival rate. Approximately 10% of cases are associated with hereditary predisposition caused by pathogenic mutations in specific cancer susceptibility genes. The disease evolves over time from precursor lesions such as pancreatic intraepithelial neoplasia and intrapapillary mucinous neoplasms. Current standard care for individuals at high risk due to hereditary predisposition or the presence of a concerning pancreatic lesion detected on imaging usually involves surveillance to monitor for changes over time. However, the chances of recurrence are up to 80%, and many precursor lesions to pancreatic cancer are microscopic and thus undetectable by imaging.
The team of researchers, led by Neeha Zaidi, MD, associate professor of oncology at the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins University, and Elizabeth Jaffee, MD, FAACR, deputy director of the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, developed a vaccine called mKRAS-VAX, which targets six of the most common KRAS mutations found in PDAC and in most pancreatic precancerous lesions. In the phase I clinical trial, 20 high-risk adults with evidence of a pancreatic lesion or cyst received the vaccine, which was administered via subcutaneous injections according to a prime-boost vaccination strategy.
Results showed that the vaccine stimulated mutant-KRAS-specific effector and central memory T-cell responses in 90% of participants. These responses remained detectable in the blood for up to two years after vaccination. After a median follow-up of 16.5 months, none of the vaccinated individuals developed cancer. The researchers also found a higher rate of cyst reduction or resolution among the vaccinated individuals (37.5%) relative to an unvaccinated cohort with similar characteristics (6.8%).
The study's findings are encouraging, but the researchers acknowledge that the trial had limitations, including the small size and the fact that it was not designed to assess the clinical efficacy of the vaccine. Larger studies are needed to demonstrate that the effect observed was in fact due to the vaccine. Additionally, the immune analysis was limited to peripheral blood, and a currently enrolling trial will assess changes in the precancer tissue to determine whether T cells generated by the vaccine are capable of infiltrating the precancer lesions.
As Elizabeth Jaffee, MD, FAACR, noted, "If we can make more progress with screening modalities to better identify who is most at risk, hopefully we can get them a vaccine early and induce an immune response that prevents them from developing pancreatic cancer."
