Bastyr/UW Oncomycology Translational Research Center

Bastyr/威斯康星大学肿瘤真菌学转化研究中心

• 批准号: 8251308
• 负责人: Mary L. Disis
• 金额: $ 13.49万
• 依托单位: BASTYR UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-09-29 至 2014-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8251308
• 关键词: Agaricales; Agonist; Asians; Blood; Cancer Patient; Center for Translational Science Activities; Chinese Traditional Medicine; Clinical; Clinical Trials; Conduct Clinical Trials; Controlled Clinical Trials; Development; Dose; Drug Kinetics; ERBB2 gene; Funding; Genes; Goals; Immune response; Immune system; Immunity; Immunologic Adjuvants; Immunologics; Immunotherapy; Instruction; Japan; Japanese Population; Lead; Licensing; Malignant neoplasm of prostate; Maximum Tolerated Dose; Measures; Metastatic Prostate Cancer; Methods; National Center for Complementary and Alternative Medicine; Oncologist; Oral; Pathway interactions; Patients; Peptides; Phase; Placebos; Polysaccharide-K; Polysaccharides; Research; Roche brand of trastuzumab; Safety; Staging; TLR4 gene; Transgenic Mice; Trastuzumab; Tumor Antigens; Tumor Markers; United States National Institutes of Health; Universities; Vaccination; Vaccines; Washington; Woman; docetaxel; immunogenicity; improved; malignant breast neoplasm; men; mouse model; overexpression; peripheral blood; phase 1 study; preclinical study; prevent; promoter; receptor; response; tumor; tumor progression

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.

目的：巴斯蒂尔大学/华盛顿大学 PCCTR 肿瘤真菌学研究中心将 中药栓菌（Tv）的免疫和抗肿瘤作用研究 药用蘑菇，在美国用于治疗癌症患者过去 6 年的研究。 我们的 NCCAM 资助的 CAM 研究发展中心 (DCRC) 让我们得出这样的结论： 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 免疫疗法，因为它通过 TOll-lil<e> 有针对性地激活先天性和适应性免疫系统 DCRC 鉴定出多糖 Krestin 受体 2 (TLR2)。 （PSK），制造并获得许可 日本作为肿瘤治疗电视产品，已完成 IND 准备，适合 NIH 临床试验。 假设；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，提高曲妥珠单抗（赫赛汀¿）的疗效，提高 HER-2/neu 的疗效 PSK 是一种 TLR2 激动剂，可增强前列腺男性的先天抗肿瘤免疫力。 PSK 与 TLR4 通路启动子多西紫杉醇联合使用将是安全的，并且不会。 与多西他赛的药理相互作用和抗肿瘤免疫反应将进一步增强 前列腺癌患者。 目标和方法：项目 1：在 Her-2/neu 小鼠模型中进行转化临床前研究 迅速开展 PSK 的 II 期对照临床试验¿作为联合给药的口服免疫佐剂 对患有晚期 HER-2/neu 阳性乳腺癌的女性 (n=30) 进行 HER2 疫苗接种治疗。 项目2：进行药代动力学研究和I期剂量递增试验以及药代动力学研究 PSK 联合多西紫杉醇治疗转移性前列腺癌 (n=32)。 意义：PSK 对于乳腺癌和前列腺癌患者来说是一种潜在的重要免疫疗法。 中心已阐明TLR作用机制，将率先在美国开展PSK临床试验 癌症患者。