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

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目及 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 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具有生存优势。 我们的研究小组已经证明，在用标准疗法治疗至最大应答或完全缓解后，用基于HER 2肽的疫苗免疫的晚期HER 2过表达乳腺癌患者具有潜在的生存优势。 最近的研究表明，在体外用曲妥珠单抗“致敏”过表达HER 2的肿瘤细胞将增强对HER 2特异性的CTL的功能。 理论上，曲妥珠单抗增强HER 2特异性CTL应答的机制可能是HER 2受体的内化、HER 2蛋白的降解和MHC-肽呈递的增加，从而导致CD 8 + HER 2特异性CTL功能的增加。 因此，曲妥珠单抗与设计用于在HLA-A2的背景下引发CTL的基于HER 2肽的疫苗的组合甚至可以进一步增强HER 2特异性CTL应答的产生，并且当用于佐剂环境中时，可能转化为晚期乳腺癌患者的改善的存活。 这是一项临床试验，旨在利用曲妥珠单抗和基于HER 2 CTL生成肽的疫苗（HER 2 CTL疫苗）之间的潜在协同效应，以增加靶向HER 2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，直至其疾病稳定，并在曲妥珠单抗维持治疗期间接受HER 2 CTL疫苗接种。

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.