Oncotarget

Research Papers:

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

Mao Lin, Mohammed Alnaggar, Shuzhen Liang, Xiaohua Wang, Yinqing Liang, Mingjie Zhang, Jibing Chen, Lizhi Niu _ and Kecheng Xu

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Oncotarget. 2017; 8:101795-101807. https://doi.org/10.18632/oncotarget.21974

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Abstract

Mao Lin1,2,*, Mohammed Alnaggar1,*, Shuzhen Liang1, Xiaohua Wang1, Yinqing Liang1, Mingjie Zhang3, Jibing Chen1,2, Lizhi Niu1,2 and Kecheng Xu1,2

1Fuda Cancer Hospital, School of Medicine, Jinan University, Guangzhou, China

2Fuda Cancer Institute, Guangzhou, China

3Hank Bioengineering Co., Ltd, Shenzhen, China

*These authors contributed equally to this work and shared the first authorship

Correspondence to:

Lizhi Niu, email: 18922210657@163.com

Jibing Chen, email: linmaogz@163.com

Mingjie Zhang, email: 307197873@qq.com

Keywords: clinical efficacy, irreversible electroporation, allogeneic natural killer cell, pancreatic cancer

Received: July 07, 2017     Accepted: September 23, 2017     Published: October 19, 2017

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: Between July 2016 and May 2017, we enrolled 71 patients who met the enrollment criteria. The patients were divided into stage III (32 patients, 17 patients received only IRE and 15 patients received IRE-NK (Irreversible electroporation- natural killer): 8 patients underwent a course of NK and 7 patients underwent ≥ 3 courses) and stage IV (39 patients, 22 patients received only IRE and 17 patients received IRE-NK: 9 patients underwent a course of NK and 8 patients underwent ≥ 3 courses). The safety and short-term effects were evaluated firstly, then the median PFS, median OS, response rate (RR) and disease control rate (DCR) were assessed.

Conclusions: Combination of irreversible electroporation and allogeneic natural killer cell immunotherapy significantly increased median PFS and median OS in stage III pancreatic cancer and extended the median OS of stage IV pancreatic cancer . Multiple allogeneic natural killer cells infusion was associated with better prognosis to stage III pancreatic cancer.


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