Purpose: To assess the effects of combining the TLR agonist activity of PSK to HER-2/neu (HER2) directed monoclonal antibody therapy using a HER2 specific vaccine for the treatment of patients with advanced stage breast cancer. We will conduct pre-clinical gene-signature biomarker work in year 1 and 2 then conduct a placebo-controlled phese II randomized controlled clinical trial in years 3 and 4. Hypothesis: PSK, when added to a HER2 vaccine will improve immune response and Survival in women with advanced HER2 overexpressing breast cancer. Methods: 1) Determine whether PSK administered concurrently with HER2-targeted vaccine can enhance tumor antigen-specific immune response and prevent or delay disease progression in neu-transgenic mice; 2) Identify a gene signature that predicts clinical response in neu-transgenic mice receiving PSK, trastuzumab, and a HER2-tergeted vaccine; and 3) Determine the safety and immunogenicity of PSK as a component of combination immunotherapy in patients with advanced stage (stage IV) breast cancer. Clinical Trial Design: 30 women with advanced HER-2/neu overexpressing breast cancer who receive trastuzumab + HER2 peptide vaccine therapy will be randomized to receive PSK or placebo orally (3000 mg/day) concomitant with vaccine therapy. Primary endpoints will be intermolecular epitope spreading, changes in TGF-b serum levels and peripheral blood biomarkers identified in neu-transgenic mice as predictive of clinical response in breast cancer patients receiving HER2 ICD vaccine.
Trametes versicolor is a immunologically active medicinal mushroom that is likely to improve the effectiveness of treatments for women with advanced breast cancer. We will investigate the effect of oral doses of PSK, a T. versicolor extract prescribed in Japan as a cancer drug, in augmenting the anticancer immune response in advanced breast cancer.
|Coy, Catherine; Standish, Leanna J; Bender, Geoff et al. (2015) Significant Correlation between TLR2 Agonist Activity and TNF-? Induction in J774.A1 Macrophage Cells by Different Medicinal Mushroom Products. Int J Med Mushrooms 17:713-22|
|Quayle, Kenneth; Coy, Catherine; Standish, Leanna et al. (2015) The TLR2 agonist in polysaccharide-K is a structurally distinct lipid which acts synergistically with the protein-bound ?-glucan. J Nat Med 69:198-208|
|Yang, Yi; Inatsuka, Carol; Gad, Ekram et al. (2014) Protein-bound polysaccharide-K induces IL-1? via TLR2 and NLRP3 inflammasome activation. Innate Immun 20:857-66|
|Engel, Abbi L; Sun, Guan-Cheng; Gad, Ekram et al. (2013) Protein-bound polysaccharide activates dendritic cells and enhances OVA-specific T cell response as vaccine adjuvant. Immunobiology 218:1468-76|
|Standish, Leanna J; Sweet, Erin; Naydis, Eleonora et al. (2013) Can we demonstrate that breast cancer ""integrative oncology"" is effective? A methodology to evaluate the effectiveness of integrative oncology offered in community clinics. Integr Cancer Ther 12:126-35|
|Inatsuka, Carol; Yang, Yi; Gad, Ekram et al. (2013) Gamma delta T cells are activated by polysaccharide K (PSK) and contribute to the anti-tumor effect of PSK. Cancer Immunol Immunother 62:1335-45|
|Wenner, Cynthia A; Martzen, Mark R; Lu, Hailing et al. (2012) Polysaccharide-K augments docetaxel-induced tumor suppression and antitumor immune response in an immunocompetent murine model of human prostate cancer. Int J Oncol 40:905-13|
|Lu, Hailing; Yang, Yi; Gad, Ekram et al. (2011) TLR2 agonist PSK activates human NK cells and enhances the antitumor effect of HER2-targeted monoclonal antibody therapy. Clin Cancer Res 17:6742-53|
|Lu, Hailing; Yang, Yi; Gad, Ekram et al. (2011) Polysaccharide krestin is a novel TLR2 agonist that mediates inhibition of tumor growth via stimulation of CD8 T cells and NK cells. Clin Cancer Res 17:67-76|