Dendritic Cell Vaccine Offers New Path in Pancreatic Cancer Treatment
A new dendritic cell vaccine has shown promising results in extending survival for pancreatic cancer patients by stimulating the immune system to fight tumor cells.
Pancreas or pancreatic cancer with organs and tumors or cancerous cells: © matthieu - stock.adobe.com
A phase 1/2 study investigating a novel dendritic cell-based immunotherapy in patients with resected pancreatic cancer met its primary end point of a 2-year relapse-free survival (RFS) rate of at least 60%, signaling the promise of this treatment course in this difficult-to-treat cancer.1
Of 28 patients with pancreatic cancer who completed the study protocol consisting of 5 dendritic cell vaccinations and after a median follow-up of 25.5 months, the RFS rate was 68% with an estimated 2-year RFS rate of 64%. Patients had undergone pancreatectomy following standard-of-care treatment and dendritic cell-based immunotherapy.
Comparatively, in the phase 3 PREOPANC trial, patients who received preoperative chemotherapy before pancreatectomy achieved a 2-year RFS rate of 40% (n = 37).2
For patients who did not receive all 5 scheduled vaccinations, 80% (n = 8) developed disease recurrence. In 20% of patients (n = 2), there were not enough dendritic cells that were cultured for 5 complete vaccinations.1
Investigators noted that there was more enriched circulating activated CD4-positive T cells following vaccination, as well as more treatment-induced immune responses in vitro.
“Advantages of [dendritic cell] vaccines over other recently used mRNA and long peptide vaccine approaches are multifactorial. [Dendritic cells] are the most professional antigen-presenting cells to stimulate both CD4 and CD8 tumor-reactive T cells,” study authors explained in findings published in the Journal of Clinical Oncology.
Along with the promising efficacy, the vaccine appeared to be well-tolerated. Grade 1 adverse events (AEs) were reported in 97% (n = 37) of patients, grade 2 in 18% (n = 7), and grade 3 in 3% (n = 1).
“In line with our previous data, treatment was associated with minimal toxicity.This is critical, considering the morbidity associated with pancreatic resection and multiagent chemotherapeutic treatment,” study authors wrote.
Study authors confirmed that a phase 2/3 trial with adjuvant dendritic cell therapy is being developed and will begin once enrollment in the PREOPANC-3 study (NCT04927780) has completed.
About the Dendritic Cell Vaccination
To create the dendritic cell vaccinations, leukapheresis was done on patients to harvest CD14-positive monocytes that were then differentiated into immature dendritic cells, loaded with an allogeneic tumor lysate-based immunotherapy, and then matured into monocyte-derived dendritic cells.3 The cells were cultured in a 9-day process, and patients started treatment after approximately 6 weeks.1
The dosing schedule of the vaccines was 3 biweekly injections with 25 x 106 dendritic cells per vaccination, with two-thirds of the volume delivered intravenously and one-third delivered intradermally. The fourth and fifth vaccinations were administered after 3 and 6 months following the third injection.
