Pancreatic cancer, especially pancreatic ductal adenocarcinoma (PDAC), remains one of the deadliest cancers. It has high recurrence rates even after curative-intent surgery and standard chemotherapy. The search for more effective strategies to reduce recurrence has led to advances in immunotherapy. One promising approach is dendritic cell-based immunotherapy. This stimulates the immune system to target and destroy residual cancer cells. A recent study investigates the potential of this therapy in patients who have undergone surgery for pancreatic cancer. The trial results, demonstrating significant improvements in recurrence-free survival (RFS) rates, suggest that this immunotherapy may offer a new strategy for preventing cancer recurrence and improving patient outcomes.
This phase I/II trial tested the efficacy of dendritic cell-based immunotherapy in preventing cancer recurrence after surgical resection of pancreatic cancer. A total of 38 patients received five doses of autologous dendritic cells pulsed with antigens shared by pancreatic cancer cells. The primary goal was to achieve a two-year recurrence-free survival (RFS) rate of at least 60%. The trial exceeded expectations. It has a 64% RFS rate and an overall survival (OS) rate of 83%. Therefore, it demonstrates the potential of this immunotherapy to significantly reduce recurrence and improve survival outcomes for patients with resected pancreatic cancer.
The study was conducted as an open-label, single-arm phase I/II trial at a single clinical center. Patients with resected pancreatic cancer who had completed standard chemotherapy and showed no evidence of recurrence were selected. Moreover, each patient underwent leukapheresis to collect immune cells, which were then cultured into dendritic cells (DCs). These DCs were loaded with an allogeneic mesothelioma tumor cell lysate that shared antigens with pancreatic cancer cells. The prepared vaccine was administered to the patients in five doses over six months. Immune responses were monitored using in vivo delayed-type hypersensitivity (DTH) tests and in vitro analysis of blood samples to assess T-cell activation.
The trial enrolled 38 patients, with a median age of 62 years (interquartile range, 55–68 years), representing a balanced gender distribution of 47% male and 53% female. All participants had undergone successful pancreatic cancer resection and completed adjuvant chemotherapy prior to enrollment. Moreover, most patients presented with localized tumors in the pancreatic head. These tumors were surgically removed through procedures such as pancreatoduodenectomy or distal pancreatosplenectomy. The study included patients with early-stage pancreatic cancer (Stage I-II) and those with more advanced disease (Stage III). Before the start of immunotherapy, patients were required to show no signs of cancer recurrence on imaging studies.
The immunotherapy consisted of five doses of autologous dendritic cells, which were harvested from each patient through a leukapheresis procedure. The DCs were cultured and pulsed with an allogeneic mesothelioma tumor lysate containing antigens that are shared by pancreatic cancer cells. This process took place over nine days, during which the dendritic cells matured and became ready for administration.
The vaccine was administered intravenously and intradermally, with three biweekly doses followed by two additional doses at three and six months, assuming no disease recurrence. Furthermore, the goal was to expose the patient’s immune system to the tumor antigens and stimulate an immune response to prevent the recurrence of pancreatic cancer. Furthermore, immune response monitoring was conducted throughout the trial using blood tests and delayed-type hypersensitivity (DTH) skin tests to measure the activation of immune cells, particularly CD4+ and CD8+ T cells.
The immunotherapy triggered significant immune responses in patients. Peripheral blood tests showed an increase in activated CD4+ T helper cells and CD8+ cytotoxic T cells. These immune cells are responsible for identifying and attacking cancer cells, suggesting that the therapy effectively engaged the immune system. Further analysis showed that central memory T cells, which are crucial for long-term immune protection, were highly activated. In vitro tests confirmed the presence of vaccine-specific immune responses, with increased production of interferon-gamma (IFN-γ), a key cytokine in cancer immunity.
Importantly, the safety profile of the immunotherapy was favorable. Most patients reported only mild side effects, such as injection site reactions and low-grade fevers, indicating a well-tolerated intervention. Only one patient experienced a grade 3 adverse event, highlighting the safety of the immunotherapy.
The study demonstrated a significant improvement in patient outcomes, with a two-year recurrence-free survival rate of 64%, surpassing the expected 60% benchmark. In addition, the two-year overall survival rate was 83%, indicating strong survival benefits for patients receiving dendritic cell-based immunotherapy. Furthermore, immunological analysis revealed robust activation of CD4+ and CD8+ T cells, which are key to long-term immune surveillance. The immunotherapy was well tolerated, with most patients experiencing only mild side effects such as localized injection reactions and low-grade fevers. Only one patient reported a grade 3 adverse event. Thus, making this approach not only effective but also safe for use in post-surgical pancreatic cancer care.
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