Dendritic Cell-Based Immunotherapy in Patients With Resected Pancreatic Cancer

J Clin Oncol. 2024 Sep 10;42(26):3083-3093. doi: 10.1200/JCO.23.02585. Epub 2024 Jul 1.

Abstract

Purpose: Immunotherapies have shown limited responses in patients with advanced pancreatic cancer. Recently, we reported that dendritic cell (DC)-based immunotherapy induced T-cell responses against pancreatic cancer antigens. The primary objective of this study was to determine the efficacy of DC-based immunotherapy to prevent recurrence of disease.

Methods: This was a single-center, open-label, single-arm, combined phase I/II trial. The primary end point was the 2-year recurrence-free survival (RFS) rate. A 2-year RFS rate of ≥60% was defined as a clinically meaningful improvement. We included patients with pancreatic cancer after resection and completion of standard-of-care (SOC) treatment without recurrent disease on cross-sectional imaging. Patients were treated with autologous DCs pulsed with an allogeneic mesothelioma tumor cell lysate, comprising antigens also expressed in pancreatic ductal adenocarcinoma.

Results: Thirty-eight patients were included in the analysis of the primary end point (47% male, 53% female). The median age was 62 years (IQR, 55-68). Twenty-eight patients (74%) received five DC vaccinations and completed the study protocol. Three patients (8%) received four vaccinations, and seven patients (16%) received three vaccinations. After a median follow-up of 25.5 months, 26 patients (68%) had not developed recurrence of disease. The estimated 2-year RFS was 64%. Vaccination led to the enrichment of circulating activated CD4+ T cells and the detection of treatment-induced immune responses in vitro. T-cell receptor-sequencing analyses of a resected solitary lung metastasis showed influx of vaccine-specific T cells.

Conclusion: This study reached its primary end point of a 2-year RFS rate of ≥60% following pancreatectomy after SOC treatment and adjuvant DC-based immunotherapy in patients with pancreatic cancer. These results warrant a future randomized trial.

Publication types

  • Clinical Trial, Phase I
  • Clinical Trial, Phase II

MeSH terms

  • Aged
  • Cancer Vaccines / administration & dosage
  • Cancer Vaccines / therapeutic use
  • Carcinoma, Pancreatic Ductal / immunology
  • Carcinoma, Pancreatic Ductal / pathology
  • Carcinoma, Pancreatic Ductal / surgery
  • Carcinoma, Pancreatic Ductal / therapy
  • Dendritic Cells* / immunology
  • Dendritic Cells* / transplantation
  • Female
  • Humans
  • Immunotherapy / methods
  • Male
  • Middle Aged
  • Neoplasm Recurrence, Local / immunology
  • Pancreatic Neoplasms* / immunology
  • Pancreatic Neoplasms* / pathology
  • Pancreatic Neoplasms* / therapy

Substances

  • Cancer Vaccines

Associated data

  • EudraCT/2018-003222-92