Bastyr/威斯康星大学肿瘤真菌学转化研究中心-猫眼课题宝

Bastyr/威斯康星大学肿瘤真菌学转化研究中心

批准号：

8146214

负责人：

Mary L. Disis

金额：

$110.62万

依托单位：

BASTYR UNIVERSITY

依托单位国家：

美国

项目类别：

财政年份：

2010

资助国家：

美国

项目状态：

已结题

起止时间：

2010-09-29 至 2014-08-31

来源：

https://reporter.nih.gov/project-details/8146214

关键词：

Agaricales Agonist American Analytical Chemistry Animals Antibody Therapy Antigen-Presenting Cells Antineoplastic Agents Antitumor Response Apoptotic Asians Award Back Biological Assay Biological Markers British Budgets CD4 Positive T Lymphocytes CD8B1 gene Cancer Patient Cells Center for Translational Science Activities Clinical Clinical Trials Clinical Trials Design Collaborations Combined Modality Therapy Conduct Clinical Trials Cytotoxic T-Lymphocytes Data Defect Dendritic Cells Disease Progression Dose Drug Formulations Drug Kinetics ERBB2 gene Effector Cell Endotoxins Epitopes Evaluation External Beam Radiation Therapy Funding Genes Glucans Goals Grant Head Heavy Metals Helper-Inducer T-Lymphocyte Human Human Activities Immune Immune response Immune system Immunity Immunologics Immunotherapy Inflammatory Interferon Type II Interleukin-2 International Japan Japanese Population Knock-out Laboratories Ligands Lymphopenia Malignant neoplasm of prostate Measurable Methodology Methods Modeling Molecular Profiling Monoclonal Antibodies Mus NK Cell Activation Natural Immunity Natural Killer Cells New York Oncologist Oral Oral Administration Outcome Pathway interactions Patients Peptide Vaccines Peripheral Blood Lymphocyte Peripheral Blood Mononuclear Cell Pesticides Pharmaceutical Chemistry Phase Phase I Clinical Trials Placebo Control Placebos Play Polysaccharide-K Polysaccharides Proteomics Radiation Radiation therapy Randomized Randomized Controlled Clinical Trials Reporting Research Role Safety Science Serum Societies Staging Study Subject T-Lymphocyte TLR2 gene TLR4 gene Testing Transgenic Mice Translating Trastuzumab Treatment Effectiveness Tumor Antigens Tumor Necrosis Factor-alpha United States National Institutes of Health Up-Regulation Vaccine Therapy Vaccines Woman Work base bench to bedside beta-Glucans breast cancer vaccine cancer cell cell mediated immune response cohort cytokine cytotoxic docetaxel fungus granulocyte immunogenic immunogenicity improved in vitro Assay in vivo interest liquid chromatography mass spectrometry malignant breast neoplasm meetings men monocyte neoplastic cell olympia oncology overexpression peripheral blood pre-clinical preclinical evaluation preclinical study pressure prevent protein expression public health relevance quality assurance response symposium tumor tumor growth

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翻译

描述(申请人提供)：目的：评估使用HER2特异性疫苗联合PSK的TLR激动剂活性与HER-2/neu(HER2)定向单克隆抗体治疗晚期乳腺癌的效果。我们将在第一年和第二年进行临床前基因签名生物标记物的工作，然后在第三年和第四年进行安慰剂对照的II期随机对照临床试验。假设：当加入HER2疫苗时，PSK将改善晚期HER2过度表达乳腺癌患者的免疫反应和生存。方法：1)确定PSK与HER2靶向疫苗同时给予是否可以增强新转基因小鼠的肿瘤抗原特异性免疫反应，防止或延缓疾病进展；2)确定预测接受PSK、曲妥珠单抗和HER2靶向疫苗的新转基因小鼠临床反应的基因标志；以及3)确定PSK作为晚期(IV期)乳腺癌联合免疫治疗的组成部分的安全性和免疫原性。临床试验设计：30名晚期HER-2/neu过表达乳腺癌患者在接受曲妥珠单抗+HER2多肽疫苗治疗的同时，随机接受PSK或安慰剂口服(3000 mg/d)，同时接受疫苗治疗。主要终点将是分子间表位扩散、在neu转基因小鼠中确定的转化生长因子-b血清水平和外周血液生物标记物的变化，以预测接受HER2 ICD疫苗的乳腺癌患者的临床反应。公共卫生相关性：杂色曲霉是一种免疫活性药用蘑菇，可能会提高晚期乳腺癌妇女的治疗效果。我们将研究口服剂量的PSK，一种在日本作为抗癌药物处方的云芝提取物，在增强晚期乳腺癌患者的抗癌免疫反应方面的效果。

英文摘要

DESCRIPTION (provided by applicant): 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.

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