Synthetic long peptide and DNA personalized cancer vaccines induce robust neoantigen-specific T cell responses in pancreatic cancer
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.
Authors
- Obi L. Griffith (ORCID: https://orcid.org/0000-0002-0843-4271)
- Nancy B. Myers
- Binghan Yan
- Ian S. Hagemann (ORCID: https://orcid.org/0000-0002-3855-9745)
- Lijin Li (ORCID: https://orcid.org/0000-0001-6203-8854)
- Andrea Wang‐Gillam (ORCID: https://orcid.org/0000-0003-0458-7614)
- Timothy P. Fleming (ORCID: https://orcid.org/0000-0002-8661-1210)
- Feng Gao (ORCID: https://orcid.org/0000-0002-1425-1623)
- Marianna B. Ruzinova (ORCID: https://orcid.org/0000-0002-0833-8335)
- S. Peter Goedegebuure (ORCID: https://orcid.org/0000-0001-7084-3378)
- Stephanie Myles
- Daniel A. Laheru (ORCID: https://orcid.org/0000-0001-6646-0200)
- Malachi Griffith (ORCID: https://orcid.org/0000-0002-6388-446X)
- Carlos Parra-López (ORCID: https://orcid.org/0000-0002-6084-8981)
- J. Li (ORCID: https://orcid.org/0000-0003-1303-9345)
- John M. Herndon (ORCID: https://orcid.org/0000-0002-8378-9654)
- Roheena Z. Panni (ORCID: https://orcid.org/0000-0002-8144-6869)
- Elizabeth M. Jaffee (ORCID: https://orcid.org/0000-0003-3841-6549)
- William G. Hawkins (ORCID: https://orcid.org/0000-0001-7087-3585)
- William E. Gillanders (ORCID: https://orcid.org/0000-0002-0465-3071)
- Julia W. Angkeow (ORCID: https://orcid.org/0009-0002-8274-1859)
- Sherri R. Davies (ORCID: https://orcid.org/0000-0002-7141-8354)
- Carl J. DeSelm (ORCID: https://orcid.org/0000-0001-7645-5798)
- Kian‐Huat Lim (ORCID: https://orcid.org/0000-0002-2766-200X)
- Robert D. Schreiber (ORCID: https://orcid.org/0000-0003-1590-2341)
- Yilin Yang (ORCID: https://orcid.org/0000-0003-4004-5126)
- Christopher A. Miller (ORCID: https://orcid.org/0000-0003-4266-6700)
- Rashmi Mishra (ORCID: https://orcid.org/0000-0001-6747-6490)
- Kartik Singhal (ORCID: https://orcid.org/0000-0002-3855-7950)
- Yik Y. L. Yu
- Darren Cullinan
- Tammi Vickery (ORCID: https://orcid.org/0009-0005-1541-1472)
- Felicia Zhang Perkins (ORCID: https://orcid.org/0000-0002-0057-5870)
- Shelby Namen (ORCID: https://orcid.org/0000-0001-5006-9020)
- Dominic Sanford
- Xiuli Zhang (ORCID: https://orcid.org/0009-0006-2464-5403)
Institutions
- James S. McDonnell Foundation (US)
- Barnes-Jewish Hospital (US)
- St. Joseph's Hospital and Medical Center (US)
- Medical University of South Carolina (US)
- Washington University in St. Louis (US)
- Universidad Nacional de Colombia (CO)
- Jewish Hospital (US)
- Sidney Kimmel Cancer Center (US)
- St. Joseph's Hospital (US)
- Sidney Kimmel Comprehensive Cancer Center (US)
Publication Details
- Journal
- Science Advances
- Published
- 2026-09-04
- DOI
- https://doi.org/10.1126/sciadv.aei1190
- Primary Topic
- Immunotherapy and Immune Responses
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- Lustgarten Foundation
- Foundation for Barnes-Jewish Hospital
- Alvin J. Siteman Cancer Center
- Centene Corporation
- National Cancer Institute
- National Institute of General Medical Sciences
- UNICO Foundation