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Data from TLR2 Agonist PSK Activates Human NK Cells and Enhances the Antitumor Effect of HER2-Targeted Monoclonal Antibody Therapy
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Data from TLR2 Agonist PSK Activates Human NK Cells and Enhances the Antitumor Effect of HER2-Targeted Monoclonal Antibody Therapy
Data from TLR2 Agonist PSK Activates Human NK Cells and Enhances the Antitumor Effect of HER2-Targeted Monoclonal Antibody Therapy
HL
Hailing Lu
Hailing Lu
YY
Yi Yang
Yi Yang
EG
Ekram Gad
Ekram Gad
CI
Carol Inatsuka
Carol Inatsuka
CW
Cynthia A. Wenner
Cynthia A. Wenner
MD
Mary L. Disis
Mary L. Disis
LS
Leanna J. Standish
Leanna J. Standish
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31 March 2023
other
Published by
American Association for Cancer Research (AACR)
https://doi.org/10.1158/1078-0432.c.6519980
Abstract
Purpose: The therapeutic effect of trastuzumab monoclonal antibody (mAb) therapy has been shown to be partially dependent on functional natural killer (NK) cells. Novel agents that enhance NK cell function could potentially improve the antitumor effect of trastuzumab. We recently identified polysaccharide krestin (PSK), a natural product extracted from medicinal mushroom Trametes versicolor, as a potent toll-like receptor 2 (TLR2) agonist. This study was undertaken to evaluate the effect of PSK on human NK cells and the potential of using PSK to enhance HER2-targeted mAb therapy.Experimental Design: Human peripheral blood mononuclear cells were stimulated with PSK to evaluate the effect of PSK on NK cell activation, IFN-γ production, cytotoxicity, and trastuzumab-mediated antibody-dependent cell-mediated cytotoxicity (ADCC). Whether the effect of PSK on NK cells is direct or indirect was also investigated. Then, in vivo experiment in neu transgenic (neu-T) mice was carried out to determine the potential of using PSK to augment the antitumor effect of HER2-targeted mAb therapy.Results: PSK activated human NK cells to produce IFN-γ and to lyse K562 target cells. PSK also enhanced trastuzumab-mediated ADCC against SKBR3 and MDA-MB-231 breast cancer cells. Both direct and interleukin-12–dependent indirect effects seem to be involved in the effect of PSK on NK cells. Oral administration of PSK significantly potentiated the antitumor effect of anti-HER2/neu mAb therapy in neu-T mice.Conclusion: These results showed that PSK activates human NK cells and potentiates trastuzumab-mediated ADCC. Concurrent treatment with PSK and trastuzumab may be a novel way to augment the antitumor effect of trastuzumab. Clin Cancer Res; 17(21); 6742–53. ©2011 AACR.
Keywords
ANTIBODY
TRASTUZUMAB
NK CELLS
AUGMENT THE ANTITUMOR
PSK ALSO ENHANCED
EFFECT OF HER2
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