Synthetic long peptide and DNA personalized cancer vaccines induce robust neoantigen-specific T cell responses in pancreatic cancer
- 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
2026-09-04
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.