S. Daniel Haldar, Assistant Professor, GI Medical Oncology at MD Anderson Cancer Center, shared on LinkedIn:
“Can we stop pancreatic cancer before it starts?
Excited to share our first-in-human study in Cancer Discovery
showing that a mutant KRAS vaccine can generate durable antigen-specific immune responses in individuals at high risk for pancreatic cancer.
Why target mutant KRAS with an off-the-shelf vaccine?
- Mutated in >90% of pancreatic cancers
- Present early in many pancreatic precursor lesions
- Shared across patients
That makes mutant KRAS an attractive target for cancer interception.
Goal: train the immune system before invasive cancer develops.
We enrolled 20 individuals with hereditary pancreatic cancer risk and a pancreatic imaging abnormality (e.g. IPMN). They received mKRAS-VAX – an off-the-shelf peptide vaccine targeting 6 common KRAS mutations – using a 4-dose prime-boost schedule.
Results:
- Self-limiting grade 1–2 vaccine-related adverse events
- Mutant KRAS-specific T-cell responses detected in 18/20 participants
- Median 18.2-fold increase in mutant KRAS-specific T cell response
- Vaccine-induced T-cell clones were detectable for up to 2 years
Although this early phase study was not designed to prove prevention, no participants developed pancreatic cancer over a median follow-up duration of 16.5 months.
Key advance: durable immunity against an early cancer driver can be safely generated in high-risk individuals.
Grateful to our study participants and to my extraordinary colleagues, collaborators, and mentors who made this work possible.”
Title: First-in-human testing of a mutant KRAS vaccine for pancreatic cancer interception in high-risk cohorts
Authors: S. Daniel Haldar, Amanda L. Huff, Hejia Henry Wang, Zirui Zhu, Maureen Berg, Jiayun Lu, Nancy Sun, Elizabeth Abou Diwan, Hassan Sinan, Christopher J. Thoburn, Matthew Z. Guo, Takeichi Yoshida, Linda C. Chu, Anna K. Ferguson, Dimitrios N. Sidiropoulos, Luciane T. Kagohara, Won Jin Ho, Katherine M. Bever, Marina Baretti, Mark Yarchoan, Daniel A. Laheru, Julie M. Nauroth, Amy M. Thomas, Hao Wang, Nilofer Saba Azad, Michael G. Goggins, Elizabeth M. Jaffee, Neeha Zaidi
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