Project #2

Trametes Versicolor-Induced Immunopotentiation in Vivo/Ex Vivo

Mushroom products advertised as immune-enhancing agents are readily available over the counter and prescribed by licensed Naturopathic and traditional Chinese medicine practitioners in North America for cancer care. While prescription of purified mushroom actives is common, complex mushroom extracts are gaining popularity in the CAM community based on the assumption that synergy between multiple active constituents in a more complex formula enhances clinical efficacy. Well-characterized Trametes versicolor (Tv) extracts, polysaccharide-Krestin (PSK) and polysaccharopeptide (PSP), are approved drugs for cancer adjunctive immunotherapy in Asia. Many published in vitro, animal and clinical studies, most conducted in Japan or China, report immune-enhancing properties of these Β-glucan-containing protein-polysaccharide fractions that potentiate antitumor activities of neutrophils, monocytes, macrophages, NK cells and T cells. Additionally, a large body of evidence suggests purified Β-glucans isolated from fungi, yeast and cereal grains induce potent antitumor immune responses.

This study explores the mechanisms of Tv-induced antitumor immunopotentiation, determining the role of Β-glucans in immune modulation and the potential for synergy of Β-glucan with other compounds in a more complex Tv extract. As a first aim, an ex vivo study was conducted in which a complex Tv extract versus PSK was orally administered to healthy subjects for 14 days. Immune parameters were assessed in peripheral blood leukocytes (PBL) from subjects before, during and after dosing. Modulation of tumor target cytotoxicity, cytokine production, and phagocytic activity by Tv and PSK were also assessed. As a second objective, the role of the Β-glucan/CR3 pathway in Tv-induced antitumor responses were examined. Finally, the potential for synergistic interactions between Β-glucan and the rest of the Tv extract were evaluated. This research has resulted in the implementation of a comprehensive immunological testing program to assess natural products alone and in combination for their potential clinical application as immunopotentiating agents.

Key Personnel:
Dennis McKenna, Co-Leader, University of Minnesota
Cynthia Wenner, Co-Leader, Bastyr University
Jeffrey Miller, Consultant, Universitiy of Minnesota