Purpose: To assess the effects of combining the TLR agonist activity of PSK to HER-2/neu (HER2) directed monoclonel 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 phase 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 advenced 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.

Public Health Relevance

Trametes versicolor is an 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.

Agency
National Institute of Health (NIH)
Institute
National Center for Complementary & Alternative Medicine (NCCAM)
Type
Research Program--Cooperative Agreements (U19)
Project #
5U19AT006028-03
Application #
8325455
Study Section
Special Emphasis Panel (ZAT1-SM (20))
Program Officer
Pontzer, Carol H
Project Start
2010-09-29
Project End
2014-08-31
Budget Start
2012-09-01
Budget End
2013-08-31
Support Year
3
Fiscal Year
2012
Total Cost
$1,207,565
Indirect Cost
$157,295
Name
Bastyr University
Department
None
Type
Organized Research Units
DUNS #
055652309
City
Kenmore
State
WA
Country
United States
Zip Code
98028