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: 7603448
• 负责人: Mary L. Disis
• 金额: $ 0.21万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-04-01 至 2007-09-16
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7603448
• 关键词: Adjuvant; CD8B1 gene; Cancer Patient; Cancer Vaccines; Cells; Clinical Trials Design; Computer Retrieval of Information on Scientific Projects Database; Data; Disease; Disease remission; ERBB2 gene; Epitopes; Frequencies; Funding; Generations; Grant; HLA-A2 Antigen; Immunotherapy; In Vitro; Institution; Maintenance; Patients; Peptide/MHC Complex; Phase; Protein Overexpression; Proteins; Research; Research Personnel; Resources; Source; Staging; Standards of Weights and Measures; Translating; Trastuzumab; Tumor Antigens; United States National Institutes of Health; Vaccination; Vaccine Design; Vaccines; chemotherapy; cytotoxic; improved; malignant breast neoplasm; neoplastic cell; peptide based vaccine; receptor; response

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 is 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.

该子项目是利用该技术的众多研究子项目之一 资源由 NIH/NCRR 资助的中心拨款提供。子项目及 研究者 (PI) 可能已从 NIH 的另一个来源获得主要资金， 因此可以在其他 CRISP 条目中表示。列出的机构是 对于中心来说，它不一定是研究者的机构。 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具有生存优势。 我们的团队已经证明，晚期 HER2 过表达乳腺癌患者在接受标准疗法的最大反应或完全缓解后，使用基于 HER2 肽的疫苗进行免疫接种具有潜在的生存优势。 最近的研究表明，体外曲妥珠单抗对 HER2 过表达肿瘤细胞的“致敏”将增强 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 蛋白的降解以及 MHC 肽呈递的增加，从而导致 CD8+ HER2 特异性 CTL 功能的增加。 因此，曲妥珠单抗与旨在在 HLA-A2 背景下引发 CTL 的 HER2 肽疫苗组合甚至可以进一步增强 HER2 特异性 CTL 反应的产生，并在辅助治疗中使用时可能转化为晚期乳腺癌患者生存率的改善。 这是一项临床试验，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，以增加针对 HER2 特定表位的 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至病情稳定，并在曲妥珠单抗维持治疗期间接受 HER2 CTL 疫苗接种。