Bastyr/UW Oncomycology Translational Research Center

目的：巴斯蒂尔大学/华盛顿大学PCCTR肿瘤研究中心将 中药杂色栓菌(TV)的免疫和抗肿瘤作用 药用蘑菇，用于治疗美国癌症患者。在过去6年的研究中 我们由NCCAM资助的CAM开发研究中心(DCRC)使我们得出结论， 日本肿瘤学家广泛使用的免疫调节蘑菇电视可能是一种有效的辅助手段 免疫治疗，因为它通过Toll-lil&lt；e；靶向激活先天和适应性免疫系统 受体2(TLR2)。DCRC鉴定了多糖克雷斯汀(PSK)，生产和许可于 日本作为一种肿瘤治疗电视产品，它是IND准备好的，适合NIH临床试验。 假说：PSK将增强肿瘤过度表达的乳腺癌患者的肿瘤免疫原性 HER-2/neu，改善曲妥珠单抗(Herceptin？)的疗效，提高HER-2/neu的疗效 多肽疫苗接种。PSK是一种TLR2激动剂，将增强前列腺癌男性患者的先天抗肿瘤免疫 癌症。PSK联合TLR4途径启动子多西紫杉醇将是安全的，但不会 与多西紫杉醇的药理相互作用和抗肿瘤免疫反应将在 前列腺癌患者。 目标和方法：项目1：在HER-2/neu小鼠模型中进行翻译的临床前研究，并 迅速进行PSK作为口服免疫佐剂联合给药的II期对照临床试验 30例晚期HER-2/neu阳性乳腺癌患者接受HER2疫苗治疗。 项目2：开展药物动力学研究和I期剂量递增试验及药代动力学研究 PSK联合多西紫杉醇治疗转移性前列腺癌32例 意义：PSK对乳腺癌和前列腺癌患者来说是一种潜在的重要免疫疗法。我们的 该中心已经阐明了TLR的作用机制，并将率先在美国进行PSK的临床试验 癌症患者。

Purpose: The Bastyr University/University of Washington PCCTR Oncomycology Research Center will investigate the immunologic and antitumor effects of Trametes versicolor (Tv) a traditional Chinese medicine medicinal mushroom, for use in the treatment of cancer patients in the US. The past 6 years of research at our NCCAM-funded Developmental Center for Research in CAM (DCRC) led us to conclude that the immunomodulating mushroom Tv, widely used by Japanese oncologists, may be an effective adjunctive immune therapy because of its targeted activation of the innate and adaptive immune system via TOll-lil<e receptors 2 (TLR2). The DCRC identified Polysaccharide Krestin¿ (PSK), manufactured and licensed in Japan as an oncologic therapy Tv product which is IND-ready and suitable for NIH clinical trials. Hypotheses; PSK will enhance tumor immunogenicity in breast cancer patients whose tumors overexpress HER-2/neu, improve the efficacy of trastuzumab (Herceptin¿) and improve the efficacy of HER-2/neu peptide vaccination. PSK, a TLR2 agonist, will augment innate antitumor immunity in men with prostate cancer. PSK combined with docetaxel, a promoter of the TLR4 pathway, will be safe and will not pharmacologically interact with docetaxel and antitumor immune response will be further enhanced in prostate cancer patients. Goals and Methods: Project 1: Conduct a translational preclinical study in the Her-2/neu mouse model and proceed rapidly to a phase Ii controlled clinical trial of PSK¿ as an oral immune adjuvant co-administered with HER2 vaccination therapy in women with advanced HER-2/neu positive breast cancer (n=30). Project 2: Conduct a pharmacokinetic study and phase I dose escalation trial and pharmacokinetic study of PSK with docetaxel to treat metastatic prostate cancer (n=32). Significance: PSK is a potentially important immune therapy for patients with breast and prostate cancer. Our center has elucidated the TLR mechanism of action and will be the first to conduct clinical trials of PSK in US cancer patients.