[Lani]

Clin Cancer Res. 2011 Sep 14. [Epub ahead of print]
TLR2 agonist PSK activates human NK cells and enhances the anti-tumor effect of HER2-targeted monoclonal antibody therapy.
Lu H, Yang Y, Gad E, Inatsuka C, Wenner CA, Disis ML, Standish LJ.
Source
Tumor Vaccine Group, University of Washington.
Abstract
PURPOSE:
The therapeutic effect of trastuzumab monoclonal antibody (mAb) therapy has been shown to be partially dependent on functional NK cells. Novel agents that enhance NK cell function could potentially improve the anti-tumor effect of trastuzumab. We recently identified polysaccharide krestin (PSK), a natural product extracted from medicinal mushroom Trametes Versicolor, as a potent TLR2 agonist. The current 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 PBMC were stimulated with PSK to evaluate the effect of PSK on NK cell activation, IFN-gamma production, cytotoxicity, and trastuzumab-mediated ADCC. Whether the effect of PSK on NK cells is direct or indirect was also investigated. Then in vivo experiment in neu transgenic mice was carried out to determine the potential of using PSK to augment the anti-tumor effect of HER2-targeted mAb therapy.

RESULTS:
PSK activated human NK cells to produce IFN-gamma and to lyse K562 target cells. PSK also enhanced trastuzumab-mediated ADCC against SKBR3 and MDA-MB-231 breast cancer cells. Both direct and IL-12-dependent indirect effects seem to be involved in the effect of PSK on NK cells. Oral administration of PSK significantly potentiated the anti-tumor effect of anti-HER2/neu mAb therapy in neu-transgenic mice.

CONCLUSIONS:
These results demonstrated that PSK activates human NK cells and potentiates trastuzumab-mediated ADCC. Concurrent treatment of PSK and trastuzumab may be a novel way to augment the anti-tumor effect of trastuzumab.

PMID: 21918170