Vollständiger Abstract
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Abstract Pancreatic ductal adenocarcinoma (PDAC) arises from precursor lesions over a decade-plus, offering a window for interception in high-risk individuals, but current surveillance detects a minority of precursors. Mutant KRAS (mKRAS) is present in most PDACs and their precursors, making it an appealing target for immune-based interception. We conducted a phase I, first-in-human study of a peptide vaccine targeting 6 common KRAS mutations (mKRAS-VAX) in 20 individuals with hereditary PDAC predisposition and a radiographic pancreatic abnormality (NCT05013216) to assess safety, immunogenicity, and T-cell persistence. Adverse events were grade 1 to 2. Vaccination elicited a significant mKRAS-specific T-cell response in 18 of 20 (90%) participants. Longitudinal T-cell receptor sequencing demonstrated persistence of vaccine-induced mKRAS-specific clonotypes for up to 2 years. Over a median follow-up of 16.5 months, no participants developed PDAC. These findings demonstrate that mKRAS-VAX is safe and generates durable T-cell responses, which support the advancement of mKRAS-targeted vaccination for PDAC interception. Significance: In high-risk individuals with hereditary predisposition to PDAC, a first-in-human peptide vaccine targeting mKRAS (mKRAS-VAX) was safe and elicited durable T-cell responses, supporting further development of mKRAS-targeted vaccination for immune interception for pancreatic precancers.
Bibliografischer Nachweis
Publikationsdaten
- Autor:innen
- 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 S. Azad, Michael G. Goggins, Elizabeth M. Jaffee, Neeha Zaidi
- Quelle
- Cancer Discovery
- Publikation
- 2026-01-01
- Band / Ausgabe
- Nicht angegeben
- Seiten
- Nicht angegeben
- ISSN / ISBN
- 2159-8274, 2159-8290
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Zitierfähiger Nachweis
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 S. Azad, Michael G. Goggins, Elizabeth M. Jaffee, Neeha Zaidi (2026). First-in-Human Testing of a Mutant KRAS Vaccine for Pancreatic Cancer Interception in High-risk Cohorts. Cancer Discovery. https://doi.org/10.1158/2159-8290.cd-25-2245