An important discovery on combination of irreversible electroporation and allogeneic natural killer cell immunotherapy for unresectable pancreatic cancer

Abstract

Purpose: To study the safety and clinical efficacy on combination of irreversible electroporation and allogeneic natural killer cell therapy for treating Stage III/IV pancreatic cancer, evaluating median progression free survival (PFS), and overall survival (OS).Results: Adverse events of all patients were limited to grades 1 and 2, including local (mainly tussis 13.4%, nausea and emesis 7.1%, pain of puncture point 29.6% and duodenum and gastric retention 4.3%) and systemic (mainly fatigue 22.3%, fever 31.6%, and transient reduction of intraoperative blood pressure 25.1% and white cell count reduction 18.3%) reactions, fever was the most frequent. The serum amylase level at 24 h and 7 d after IRE was not significantly changed compared to those before IRE (P > 0.05). CA19-9 value was lower in IRE-NK group than in IRE at 1 month after treatment (P < 0.05). After a median follow-up of 7.4 months (3.6-11.2 months): in stage III group, median PFS was higher in IRE-NK group (9.3 months) than in IRE group (8.1 months, P = 0.0465), median OS was higher in IRE-NK (13.2 months) than in IRE (11.4 months, P = 0.0411), and median PFS was higher in who received multiple NK than single NK (9.8 months vs.8.1 months, P = 0.0423, respectively), median OS who received multiple NK was higher than single NK (13.9 months vs.12.3 months, P = 0.0524, respectively), the RR in IRE-NK (63.2%) was higher than in IRE (50.0%, P < 0.05); in stage IV group, median OS was higher in IRE-NK (9.8 months) than in IRE (8.7 months, P = 0.0397), the DCR in IRE-NK (66.7%) was higher than in IRE (42.9%, P < 0.05). Materials and Methods

Natural Killer Cells in Liver Disease and Hepatocellular Carcinoma and the NK Cell-Based Immunotherapy

“…Lin et al had reported that percutaneous cryoablation combined with allogeneic NK adoptive transfer significantly increased the median progression-free survival of advanced HCC patients [ 75 ]. And multiple allogeneic NK cell infusion was associated with better prognosis in advanced cancers, including advanced HCC [ 75 ] and stage III pancreatic cancer [ 76 ]. Allogeneic NK cell immunotherapy for advanced non-small-cell lung cancer also showed a significant benefit in clinic [ 77 ].…”

Irreversible Electroporation for Locally Advanced Pancreatic Cancer

“…63 Furthermore, in a clinical study for unresectable LAPC, a combination of IRE and allogeneic natural killer cells achieved significant improvement in OS over IRE alone. 64,65 Although these are optimistic results, more research is imperative to determine Table 2 Overview overall survival after pancreatic irreversible electroporation (IRE) for locally advanced pancreatic cancer (LAPC). Overview of open, laparoscopic and percutaneous pancreatic IRE studies and their survival outcomes (median, in months).…”

Palliative therapy in pancreatic cancer—interventional treatment with radiofrequency ablation/irreversible electroporation

“…However, opposite results came afterwards from studies on animal models, that claimed that IRE can trigger the immune response, even stronger than RFA in this sense (53). Furthermore, recently Lin et al discovered that the combination of IRE and allogeneic NK cell played a synergistic effect, enhancing the immune function of patients demonstrating a fruitful post-IRE immunomodulation that can amplify systemically the results obtained locally (54). These controversial results rely on the complex interaction between the immune system and PC (55).…”