Experimental KRAS vaccine safely generates durable immune response against pancreatic cancer
· News-MedicalThis study represents what is believed to be the first-in-human demonstration that a KRAS-targeted vaccine can safely generate lasting immune responses, potentially preventing development of the cancer in people at risk.
Pancreatic ductal adenocarcinoma often develops over many years from precursor lesions, such as pancreatic cysts, creating a potential window for interventions that could prevent cancer from forming. KRAS mutations are present in most pancreatic cancers and most pancreatic precancerous lesions. The vaccine causes the immune system to recognize and destroy cells carrying these mutations before they can develop into cancer.
The study evaluated mKRAS-VAX, a peptide-based vaccine targeting the six most common KRAS mutations found in pancreatic cancer. Twenty participants with a hereditary predisposition to pancreatic cancer and a pancreatic abnormality identified through imaging received the vaccine between April 2022 and February 2026. Four doses of vaccine were administered over 13 weeks. Researchers monitored participants for safety and immune responses through blood testing and follow-up evaluations.
Researchers found that 18 of 20 participants, or 90%, developed a significant immune response to the vaccine. Participants experienced a median 18.2-fold increase in mutant KRAS-specific T-cell responses, indicating that the vaccine successfully activated immune cells capable of recognizing KRAS mutations. Additional analyses showed that the vaccine generated both CD4-positive and CD8-positive T-cell responses and produced memory T cells that persisted over time. Vaccine-induced mutant KRAS-specific T-cell clones remained detectable for as long as two years after vaccination.
Researchers also conducted an exploratory analysis of pancreatic cysts in participants who had follow-up imaging available. Five of the 20 participants in the study experienced complete radiographic resolution of small pancreatic cysts, while three others experienced partial regression. The remaining cysts remained stable.
The investigators note that the study was designed primarily to evaluate safety and immune responses and was not intended to determine whether the vaccine prevents pancreatic cancer. They caution that the small study size and relatively short follow-up period limit conclusions regarding clinical efficacy.
Elizabeth Jaffee, M.D., deputy director of the Johns Hopkins Kimmel Cancer Center, the Dana and Albert "Cubby" Broccoli Professor of Oncology, co-director of the Skip Viragh Center for Pancreatic Cancer, associate director of the Bloomberg~Kimmel Institute for Cancer Immunotherapy, and co-senior author of the studyThis is just the beginning, but the findings suggest that the immune system is getting activated. We have more work to do, but this is a good start aimed at prevention, which no one had thought about doing before."
"The ability to vaccinate people at risk early to try to prevent them from developing cancer in the future is an important opportunity," adds Jaffee.
The researchers have initiated an additional study to evaluate the effects of the vaccine in patients with high-risk pancreatic cysts undergoing surgical resection. This new study will enable them to see how vaccine-induced immune cells directly affect precancerous pancreatic tissue.
In addition to Jaffee, Zaid and Goggins, other researchers participating in the study were S. Daniel Haldar, Amanda L. Huff, Hejia Henry Wang, Zirui Zhu, Maureen Berg, Jiayun Lu, Nancy Sun, Elizabeth Abou Diwan, Hassan Sinan, Christopher Thoburn, Matthew Guo, Takeichi Yoshida, Linda Chu, Anna Ferguson, Dimitrios Sidiropoulos, Luciane Kagohara, Won Jin Ho, Katherine Bever, Marina Baretti, Mark Yarchoan, Daniel Laheru, Julie Nauroth, Amy Thomas, Hao Wang and Nilofer Azad.
Huff, Jaffee, Yarchoan, and Zaidi are founders of, and hold equity in, Adventris Pharmaceuticals. Jaffee and Zaidi also serve as consultants to the entity. Yarchoan serves as the Chief Medical Officer of the entity. Further, Adventris Pharmaceuticals has licensed a technology described in this study from the Johns Hopkins University. As a result of that agreement, Huff, Jaffee, Yarchoan, Zaidi and the University are entitled to royalty distributions related to technology described in the study discussed in this press release.
Source:
Journal reference: