Abstract IA005: Mutant KRAS-Targeted Vaccines for Cancer Treatment and Interception

Abstract Pancreatic ductal adenocarcinoma (PDAC) is an aggressive malignancy with a 5-year survival rate of only 13%. Mutant KRAS (mKRAS) is an oncogenic driver found in >90% of PDACs and the majority of associated precancer lesions, including >90% of PanINs and 80-90% of IPMNs. As a shared neoantigen thought to be the initiating genetic event driving precancer lesions and maintaining the PDAC malignancy phenotype, mKRAS is an attractive target for both precision immunotherapy of established PDAC, and for immune interception strategies in the precancer setting. We previously reported that vaccination against mKRAS can slow the progression of early PanIN lesions to invasive cancer and prolong survival in a KRASG12D-driven mouse model of PDAC. More recently, we reported the safety and induction of mKRAS-specific T cell responses with a first in patients mKRAS synthetic long peptide (SLP) vaccine given with ipilimumab and nivolumab to patients following surgical resection and adjuvant chemotherapy for localized PDAC. Patients demonstrating mKRAS immunity had associated prolonged recurrence-free survival. This SLP vaccine consisting of six 21-amino acid peptides, each carrying one of 6 mutations in the middle of the SLP, is now in testing for interception of PanINs and IPMNs. The results of these studies and future implications will be discussed. Citation Format: Elizabeth M. Jaffee. Mutant KRAS-Targeted Vaccines for Cancer Treatment and Interception [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: RAS Oncogenesis and Therapeutics; 2026 Mar 5-8; Los Angeles, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(5_Suppl_1):Abstract nr IA005.