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Augmenting immunity via HER2-targeted immunotherapy and PSK M.Disis/L.Standish

通过 HER2 靶向免疫疗法和 PSK M.Disis/L.Standish 增强免疫力

基本信息

批准号：
8093334
负责人：
LEANNA J STANDISH
金额：
$ 59.1万
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
起止时间：
2010-10-01 至 2011-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8093334
关键词：
Adjuvant Agaricales Agonist Animal Model Antineoplastic Agents Biological Factors Biological Markers Blood Cancer Patient Clinical Clinical Trials Clinical Trials Design Complementary and alternative medicine Development Disease Disease Progression Dose Epitopes Genes Genetic Immune response Immunity Immunotherapy Japan Lead Mammary Neoplasms Methods Monoclonal Antibodies Monoclonal Antibody Therapy Mus NIH Program Announcements Oral Patients Peptide Vaccines Phase Placebo Control Placebos Polysaccharide-K Randomized Randomized Controlled Clinical Trials Residual Cancers Residual Neoplasm Safety Secondary to Serum Staging T-Lymphocyte Testing Toll-Like Receptor 2 Toll-like receptors Transgenic Mice Translational Research Trastuzumab Treatment Effectiveness Tumor Antigens Vaccine Therapy Vaccines Woman Work base immunogenicity improved malignant breast neoplasm overexpression patient population peripheral blood pre-clinical preclinical study prevent response tumor tumor progression

项目摘要

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

目的：评价将PSK的TLR激动剂活性与HER-2/neu(HER2)单抗联合治疗晚期乳腺癌的疗效。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PSK加入HER2疫苗时，将改善晚期HER2过度表达乳腺癌患者的免疫反应和存活率。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名接受曲妥珠单抗+HER2多肽疫苗治疗的晚期HER-2/neu过表达乳腺癌患者将随机接受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。