Dataset Information

IL-21 Enhances Natural Killer Cell Response to Cetuximab-Coated Pancreatic Tumor Cells.

ABSTRACT:

Purpose

Alternative strategies to EGFR blockage by mAbs is necessary to improve the efficacy of therapy in patients with locally advanced or metastatic pancreatic cancer. One such strategy includes the use of NK cells to clear cetuximab-coated tumor cells, as need for novel therapeutic approaches to enhance the efficacy of cetuximab is evident. We show that IL-21 enhances NK cell-mediated effector functions against cetuximab-coated pancreatic tumor cells irrespective of KRAS mutation status.

Experimental design

NK cells from normal donors or donors with pancreatic cancer were used to assess ADCC, IFN-γ release, and T-cell chemotaxis toward human pancreatic cancer cell lines. The in vivo efficacy of IL-21 in combination with cetuximab was evaluated in a subcutaneous and intraperitoneal model of pancreatic cancer.

Results

NK cell lysis of cetuximab-coated wild-type and mutant kras pancreatic cancer cell lines were significantly higher following NK cell IL-21 treatment. In response to cetuximab-coated pancreatic tumor cells, IL-21-treated NK cells secreted significantly higher levels of IFN-γ and chemokines, increased chemotaxis of T cells, and enhanced NK cell signal transduction via activation of ERK and STAT1. Treatment of mice bearing subcutaneous or intraperitoneal EGFR-positive pancreatic tumor xenografts with mIL-21 and cetuximab led to significant inhibition of tumor growth, a result further enhanced by the addition of gemcitabine.

Conclusions

These results suggest that cetuximab treatment in combination with IL-21 adjuvant therapy in patients with EGFR-positive pancreatic cancer results in significant NK cell activation, irrespective of KRAS mutation status, and may be a potential therapeutic strategy. Clin Cancer Res; 23(2); 489-502. ©2016 AACR.

SUBMITTER: McMichael EL

PROVIDER: S-EPMC5241232 | biostudies-literature | 2017 Jan

REPOSITORIES: biostudies-literature

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Publications

IL-21 Enhances Natural Killer Cell Response to Cetuximab-Coated Pancreatic Tumor Cells.

McMichael Elizabeth L EL Jaime-Ramirez Alena Cristina AC Guenterberg Kristan D KD Luedke Eric E Atwal Lakhvir S LS Campbell Amanda R AR Hu Zhiwei Z Tatum Armika S AS Kondadasula Sri Vidya SV Mo Xiaokui X Tridandapani Susheela S Bloomston Mark M Ellison E Christopher EC Williams Terence M TM Bekaii-Saab Tanios T Carson William E WE

Clinical cancer research : an official journal of the American Association for Cancer Research 20160719 2

<h4>Purpose</h4>Alternative strategies to EGFR blockage by mAbs is necessary to improve the efficacy of therapy in patients with locally advanced or metastatic pancreatic cancer. One such strategy includes the use of NK cells to clear cetuximab-coated tumor cells, as need for novel therapeutic approaches to enhance the efficacy of cetuximab is evident. We show that IL-21 enhances NK cell-mediated effector functions against cetuximab-coated pancreatic tumor cells irrespective of KRAS mutation sta ...[more]

PMID: 27435400

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Dataset Information

IL-21 Enhances Natural Killer Cell Response to Cetuximab-Coated Pancreatic Tumor Cells.

Purpose

Experimental design

Results

Conclusions

Publications

IL-21 Enhances Natural Killer Cell Response to Cetuximab-Coated Pancreatic Tumor Cells.

Similar Datasets

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