Breakthrough Pancreatic Cancer Vaccine Demonstrates Efficacy in Phase 1 Clinical Trial

A peptide-based vaccine slowed pancreatic lesions progression to tumors in high-risk individuals.

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Pancreatic ductal adenocarcinoma (PDAC), the most prevalent form of pancreatic cancer, is frequently undiagnosed until late stages due to minimal early symptoms, resulting in poor survival rates. However, PDAC tumors develop gradually over decades from benign cysts or lesions. As 10% of PDAC cases have genetic predispositions, this presents an opportunity for early interventions to delay or prevent cancer progression.1

A Johns Hopkins University research team investigated a vaccine targeting the most common KRAS gene mutations, which frequently drive PDAC and early lesions. In a Phase 1 clinical trial, the vaccine stimulated protective T cell responses and delayed lesion progression to cancer in high-risk participants.4 Published in Cancer Discovery, these findings highlight the vaccine’s potential for broader therapeutic application.

“The immune system activation observed here is a critical first step,” stated Elizabeth Jaffee, an oncologist and coauthor, in a press release.

Researchers identified six prevalent mutant KRAS (mKRAS) variants in PDAC tumors and incorporated them into a peptide-based vaccine. Earlier studies confirmed the vaccine’s safety and ability to generate mKRAS-specific T cells in PDAC patients undergoing treatment.5

In this trial, 20 individuals with genetic PDAC risk and non-cancerous pancreatic lesions received the vaccine in four doses, including a booster four weeks after the final dose. Blood samples collected at each visit and four weeks post-vaccination assessed immune responses.

Participants reported only mild, self-resolving side effects like fatigue and flu-like symptoms. Immune analyses revealed a median 18.2-fold increase in T cell responses targeting all mKRAS vaccine peptides, with half showing strong reactions to all six antigens.

Over a 16.5-month follow-up, none of the vaccinated patients experienced progression of their lesions to cancer. Three individuals saw their cysts resolve entirely, while three others experienced lesion regression; the remainder remained stable. In contrast, unvaccinated individuals showed higher lesion progression rates during the same period.

Follow-up analyses indicated that vaccinated patients maintained CD4+ and CD8+ T cell memory, including effector and central memory subsets. Though these cell populations declined over time, their reactivation potential upon antigen re-exposure remained robust in laboratory testing.

“This study offers the first evidence that vaccines can intercept pancreatic cancer in human patients,” noted Neeha Zaidi, another study coauthor, in the same release.

Disclosure of Conflict of Interest: Elizabeth Jaffee and Neeha Zaidi are founders and consultants for Adventris Pharmaceuticals, where they also hold equity. Some technology used in this research was licensed by Adventris Pharmaceuticals from Johns Hopkins University.

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