Dendritic Cell-Based Immunotherapy in Patients With Resected Pancreatic Cancer

Our plain-English summary of Dendritic Cell-Based Immunotherapy in Patients With Resected Pancreatic Cancer, by F.R. van 't Land, M. Willemsen, K. Bezemer, et al (Journal of Clinical Oncology, 2024).

The study

• Authors: F.R. van 't Land, M. Willemsen, K. Bezemer, S.H. van der Burg, T.P.P. van den Bosch, M. Doukas, A. Fellah, P.M. Kolijn, A.W. Langerak, M. Moskie, E. van der Oost, N.E.M. Rozendaal, S.J. Baart, J.G.J.V. Aerts, C.H.J. van Eijck
• Journal: Journal of Clinical Oncology
• Published: 2024;42(26):3083-3093
• Cited by: 43 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

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.

In plain English

This was a single-center, open-label, single-arm phase I/II trial in the Netherlands. It tested a dendritic cell vaccine after surgical removal of pancreatic cancer in people who had completed or been offered standard treatment (5 of 38 received no chemotherapy) and had no sign of recurrence. It was not a study of asbestos exposure. The vaccine was made from each patient's own immune cells loaded with material from mesothelioma tumor cells, which the authors said contains antigens also found in pancreatic cancer. Of 43 patients screened, 38 were analyzed. After a median follow-up of 25.5 months, the estimated 2-year recurrence-free survival rate was 64%, above the 60% target. The estimated 2-year survival rate was 83%, and 12 of 38 patients had a recurrence. One patient had a possibly treatment-related grade 3 side effect, shortness of breath. Blood tests in 23 patients showed activation of CD4+ T cells. The authors concluded that the results warrant a randomized trial. They noted that patients joined a median of 8 months after surgery, introducing immortal time bias, and that the benchmark came from a historical group.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: single-center, open-label, single-arm, combined phase I/II clinical trial
• Who was studied: 43 patients with resected pancreatic cancer screened between February 2019 and November 2022 at a single center (Erasmus MC, Rotterdam, the Netherlands). Eligibility required completed or offered standard-of-care treatment and no signs of recurrence on imaging. 38 patients (47% male, 53% female) were included in the primary end point analysis: 10 from the phase I safety cohort and 28 from the phase II expansion cohort. Five of the 38 received no chemotherapy.
• Exposure: Not an asbestos exposure. Treatment was autologous dendritic cells loaded with an allogeneic mesothelioma tumor cell lysate. Patients received three vaccinations two weeks apart of about 25 million cells each, with fourth and fifth vaccinations 3 and 6 months after the third if there was no recurrence.
• Main results:
  • In the 38 analyzed patients, after a median follow-up of 25.5 months, the estimated 2-year recurrence-free survival rate was 64% and the estimated 2-year overall survival rate was 83%
  • 12 of 38 patients (31.6%) developed recurrence: six local, four distant, two both
  • Side effects among the 38 patients: 37 (97%) had a grade 1 related adverse event, seven (18%) a grade 2 related adverse event, and one (3%) a grade 3 related adverse event (possibly related shortness of breath)
  • All 38 patients developed a positive skin test reaction to the vaccine
  • In flow cytometry of 23 expansion-cohort patients, vaccination was followed by activation of peripheral blood CD4+ T cells, mainly central memory cells, without activation of regulatory CD4+ T cells
  • In one patient who had a solitary lung metastasis removed after the vaccine, 13 T-cell receptor clonotypes were shared between the vaccine skin-test biopsy and the lung metastasis but were absent from the original pancreatic tumor
• The authors' conclusion: The authors concluded that the study met its primary end point and that, despite its limitations, the results warrant a future randomized trial of adjuvant dendritic cell therapy in resected pancreatic cancer
• Limitations the authors state:
  • Patients enrolled a median of 8 months after surgery, which screened out those at high risk of early recurrence and introduces immortal time bias
  • Using a historical subgroup as the 2-year recurrence-free survival benchmark is challenging
  • The cohort varied in disease stage, prior treatment and other illnesses, which could affect outcomes
  • It is unknown which antigens the immune response was directed against
  • With a single-arm design in patients without active disease, separating treatment effects from tumor biology is difficult

Topics

Medical terms in this study, explained in our Lexicon: Immunotherapy, Recurrence-Free Survival, Mesothelioma, Adenocarcinoma, Metastasis.

Related studies

• Adjuvant dendritic cell based immunotherapy (DCBI) after cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) for peritoneal mesothelioma, a phase II single centre open-label clinical trial: rationale and design of the MESOPEC trial — N.L. de Boer, J.P. van Kooten, et al. (2019)
• Dendritic cell-based immunotherapy in mesothelioma — R. Cornelissen, L.A. Lievense, et al. (2012)
• Adjuvant dendritic cell-based immunotherapy after cytoreductive surgery and hyperthermic intraperitoneal chemotherapy in patients with malignant peritoneal mesothelioma: a phase II clinical trial — M.V. Dietz, K.L.A. Quintelier, et al. (2023)
• Exercise Boosts the Immune System and Enhances Immunotherapy Responses in Pancreatic Cancer and Mesothelioma — B. Hapuarachi, S. Danson, et al. (2026)
• WT1-mRNA dendritic cell vaccination of patients with glioblastoma multiforme, malignant pleural mesothelioma, metastatic breast cancer, and other solid tumors: type 1 T-lymphocyte responses are associated with clinical outcome — Z.N. Berneman, M. De Laere, et al. (2025)
• Autologous Dendritic Cell Therapy in Mesothelioma Patients Enhances Frequencies of Peripheral CD4 T Cells Expressing HLA-DR, PD-1, or ICOS — P.L. de Goeje, Y. Klaver, et al. (2018)

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