PHASE I-II STUDY OF COMBINATION IMMUNOTHERAPY FOR HER-2/NEU CYTOTOXIC T CELLS

HER-2/NEU 细胞毒性 T 细胞联合免疫治疗的 I-II 期研究

• 批准号: 7379340
• 负责人: Mary L. Disis
• 金额: $ 4.05万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-04-01 至 2007-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7379340
• 关键词: PHASE; II; STUDY; COMBINATION; IMMUNOTHERAPY

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Data from tumor vaccine studies now indicate there might be survival advantages for patients who have received tumor-antigen specific vaccinations. Our group has demonstrated a potential survival advantage for patients with advanced stage HER2 overexpressing breast cancer immunized with a HER2 peptide-based vaccine after being treated to maximal response or complete remission with standard therapy. Recent studies have demonstrated that "sensitization" of HER2 overexpressing tumor cells with trastuzumab, in vitro, will enhance the function of CTL specific for HER2. Theoretically, the mechanism of trastuzumab's enhancement of a HER2 specific CTL response might be the internalization of the HER2 receptor, degradation of the HER2 protein, and increased MHC-peptide presentation with a resultant increase in CD8+ HER2 specific CTL function. Thus, combination of trastuzumab with HER2 peptide based vaccine designed to elicit CTL in the context of HLA-A2 may even further enhance the generation of a HER2 specific CTL response and potentially translate into improved survival for advanced stage breast cancer patients when used in the adjuvant setting. This proposal outlines a clinical trial designed to utilize the potential synergistic effect between trastuzumab and a HER2 CTL generating peptide based vaccine (HER2 CTL vaccine) in order to increase CTL precursor frequencies that target HER2 specific epitopes. Patients with advanced stage breast cancer will be treated until their disease stabilizes with chemotherapy and trastuzumab and while on maintenance trastuzumab receive vaccinations with a HER2 CTL vaccine.

本子项目是利用由NIH/NCRR资助的中心赠款提供的资源的众多研究子项目之一。子项目和研究者（PI）可能已经从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。列出的机构是中心的，不一定是研究者的机构。来自肿瘤疫苗研究的数据现在表明，接受肿瘤抗原特异性疫苗接种的患者可能有生存优势。我们的研究小组已经证明，在接受标准治疗达到最大反应或完全缓解后，接受HER2肽基疫苗免疫的晚期HER2过表达乳腺癌患者具有潜在的生存优势。最近的研究表明，体外使用曲妥珠单抗“致敏”HER2过表达的肿瘤细胞可以增强HER2特异性CTL的功能。理论上，曲妥珠单抗增强HER2特异性CTL反应的机制可能是HER2受体的内化、HER2蛋白的降解和mhc肽的增加，从而导致CD8+ HER2特异性CTL功能的增加。因此，曲妥珠单抗与基于HER2肽的疫苗联合使用，可以在HLA-A2环境下引发CTL，甚至可以进一步增强HER2特异性CTL反应的产生，并可能在辅助治疗中提高晚期乳腺癌患者的生存率。该建议概述了一项临床试验，旨在利用曲妥珠单抗和HER2 CTL生成肽疫苗（HER2 CTL疫苗）之间的潜在协同效应，以增加靶向HER2特异性表位的CTL前体频率。晚期乳腺癌患者将接受化疗和曲妥珠单抗治疗，直到病情稳定，在曲妥珠单抗维持期间，接受HER2 CTL疫苗接种。