Abstract 1806: TLR2 agonist PSK activates NK cells and enhances the anti-tumor effect of HER2-targeted monoclonal antibody therapy

Abstract

Abstract Purpose: The therapeutic effect of trastuzumab, the anti-HER2 monoclonal antibody (mAb), is dependent on functional NK cells which mediates antibody-dependent cell-mediated cytotoxicity (ADCC). Novel agents that enhance NK cell function could potentially improve the therapeutic effect of trastuzumab. We recently identified polysaccharide krestin (PSK), a natural product extracted from medicinal mushroom, as a novel TLR2 agonist. The current study was undertaken to evaluate the effect of PSK on human NK cells and the potential of 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 and IFN-g secretion. K 562 was used as a target to measure the lytic function of NK cells. Effect of PSK on ADCC was also measured using trastuzumab-coated SKBR3 and MDA-MB-231 breast cancer cells. Finally, in vivo experiment in neu transgenic mice was carried out to determine the potential of PSK to augmented HER2-targeted mAb therapy. Results: PSK upregulated the expression of activation markers, CD25 and CD69, on NK cells, and stimulated IFN-g production by NK cells. The cytolytic potential of NK cells, as shown by CD107a degranulation and lysis of K562, was also augmented by PSK treatment. PSK enhanced trastuzumab-mediated ADCC in lysing both SKBR3 and MDA-MB-231 breast cancer cells. In vivo treatment in neu transgenic mice showed that oral administration of PSK significantly potentiated the anti-tumor effect of anti-rat neu/HER2 mAb therapy. Conclusion: These results demonstrated that natural product 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. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 1806. doi:10.1158/1538-7445.AM2011-1806