期刊
FRONTIERS IN IMMUNOLOGY
卷 6, 期 -, 页码 -出版社
FRONTIERS MEDIA SA
DOI: 10.3389/fimmu.2015.00162
关键词
Hsp70-based immunotherapy; NSCLC patients; radiochemotherapy clinical trial; clinical phase II; NK cells
类别
资金
- DFG - Cluster of Excellence: Munich-Centre for Advanced Photonics (MAP) [SFB824/2, DFG - INST95/980-1FUGG, DFG - INST411/37-1FUGG]
- German Federal Ministry of Education and Research (BMBF) [0313909]
- m<SUP>4</SUP> - Cluster of Excellence: Personalized Medicine (BMBF) [16EX1021C, 16GW0030]
- Kompetenzverbund Strahlenforschung [02NUK038A]
- Innovative Therapies [01GU0823]
- EU-CELLEUROPE [315963]
- Wilhelm Sander-Stiftung [2012.078.1]
Heat shock protein 70 (Hsp70) is frequently overexpressed in tumor cells. An unusual cell surface localization could be demonstrated on a large variety of solid tumors including lung, colorectal, breast, squamous cell carcinomas of the head and neck, prostate and pancreatic carcinomas, glioblastomas, sarcomas and hematological malignancies, but not on corresponding normal tissues. A membrane (m)Hsp70-positive phenotype can be determined either directly on single cell suspensions of tumor biopsies by flow cytometry using cmHsp70.1 monoclonal antibody or indirectly in the serum of patients using a novel lipHsp70 ELISA. A mHsp70-positive tumor phenotype has been associated with highly aggressive tumors, causing invasion and metastases and resistance to cell death. However, natural killer (NK), but not T cells were found to kill mHsp70-positive tumor cells after activation with a naturally occurring Hsp70 peptide (TKD) plus low dose 11,2 (TKD/11,2). Safety and tolerability of ex vivo TKD/11,2 stimulated, autologous NK cells has been demonstrated in patients with metastasized colorectal and non-small cell lung cancer (NSCLC) in a phase I clinical trial. Based on promising clinical results of the previous study, a phase 11 randomized clinical study was initiated in 2014. The primary objective of this multicenter proof-of-concept trial is to examine whether an adjuvant treatment of NSCLC patients after platinum-based radiochemotherapy (RCTx) with TKD/11,2 activated, autologous NK cells is clinically effective. As a mHsp70-positive tumor phenotype is associated with poor clinical outcome only mHsp70-positive tumor patients will be recruited into the trial. The primary endpoint of this study will be the comparison of the progression-free survival of patients treated with ex vivo activated NK cells compared to patients who were treated with RCTx alone. As secondary endpoints overall survival, toxicity, quality-of-life, and biological responses will be determined in both study groups.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据