Synthetic long peptide and DNA personalized cancer vaccines induce robust neoantigen-specific T cell responses in pancreatic cancer.

Authors

Felicia Zhang Perkins, Xiuli Zhang, Yik Yeung Lawrence Yu, Yilin Yang, Darren Cullinan, Kartik Singhal, Carlos A Parra-Lopez, Christopher A Miller, Binghan Yan, Julia W Angkeow, Jinglun Li, Nancy B Myers, Tammi Vickery, John Herndon, Rashmi Mishra, Stephanie Myles, Dominic Sanford, Elizabeth M Jaffee, Daniel A Laheru, Andrea Wang-Gillam, Marianna B Ruzinova, Ian S Hagemann, Sherri R Davies, Timothy P Fleming, Shelby Namen, Carl J DeSelm, Lijin Li, Roheena Z Panni, Feng Gao, Kian-Huat Lim, Obi L Griffith, Malachi Griffith, Robert D Schreiber, S Peter Goedegebuure, William G Hawkins, William E Gillanders

Published in

Science advances. Volume 12. Issue 36. Pages eaei1190. Sep 04, 2026. Epub Sep 04, 2026.

Abstract

Pancreatic ductal adenocarcinoma (PDAC) is unresponsive to standard immunotherapies despite harboring cancer neoantigens capable of eliciting T cell responses. We completed two phase 1 clinical trials (NCT03956056 and NCT03122106) evaluating safety and immunogenicity of synthetic long peptide (SLP) and DNA personalized cancer vaccines (PCVs). PCVs were administered after resection and adjuvant chemotherapy. Tumor/normal whole-exome sequencing, RNA sequencing, and pVACtools were used to identify and prioritize candidate PCV neoantigens. PCVs were well tolerated without any grade ≥3 adverse events. Neoantigen-specific responses were demonstrated by interferon-γ enzyme-linked immunospot and intracellular cytokine staining. Expanded T cell receptor clonotypes were sequenced and transduced into autologous peripheral blood mononuclear cells to confirm neoantigen specificity. When compared with a contemporaneous institutional propensity-matched cohort, PCV patients demonstrated a trend toward prolonged median overall survival (4.4 versus 3.5 years, log-rank P = 0.23). Overall, PDAC PCVs are safe and feasible and elicit polyclonal T cell responses, linking prioritized cancer neoantigens to functional antitumor immunity.

PMID:
42696575
Bibliographic data and abstract were imported from PubMed on 05 Sep 2026.

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