PATIENTS' IMMUNE RESPONSES

这些研究的主要目的是评估体液免疫和 结直肠癌（CRC）患者对 接种（在项目3中）表达 CRC相关抗原GA 733（AdGA 733 -2）。接种疫苗的评价 患者对AdGA 733 -2的免疫反应将使我们了解 可能导致潜在临床效应的免疫学机制 疫苗患者免疫应答的两种表位分析都将在 进行鉴定GA 733抗原（Ag）片段， 在未来的研究中，与全长Ag相比，疫苗具有上级优势。 探讨腺病毒GA 733 -2免疫大肠癌细胞的体液免疫应答 患者，将检测诱导抗体与GA 733 Ag、Ag- 阳性肿瘤细胞，对Ag阳性肿瘤的细胞毒反应性 细胞和表位特异性（使用GA 733 Ag衍生的片段， 项目1）。评估Ad GA 733 -2中T辅助细胞的诱导 免疫患者对GA 733 Ag的增殖淋巴细胞反应 将被证明，随后进行功能和表型分析， 增殖的细胞。评价细胞毒性T淋巴细胞（CTL） 在接种疫苗的患者中，针对GA 733 Ag的CTL将被免疫。 鉴定 作为CRC患者研究的一个重要相关因素， 约50%的人对GA 733 Ag结合抗体的应答 健康的个体。了解这些疾病的抗原特异性和病因学 免疫反应对于理解免疫系统至关重要 接种以下疫苗的CRC患者中免疫应答诱导的机制 AdGA 733 -2。 拟议的研究将确定免疫原性和机制 研究最充分的一种CRC相关抗原在患者中的作用。的 GA 733 Ag的免疫原性表位/片段的鉴定将 为CRC提供新的、潜在改进的免疫疗法。

The major goal of the proposed studies is to evaluate humoral and cellular immune responses of colorectal cancer (CRC) patients to vaccinations (in Project 3) with recombinant adenovirus expressing the CRC-associated antigen GA733 (AdGA733-2). Evaluation of vaccinated patients' immune responses to AdGA733-2 will give insight into the immunological mechanism(s) that may underlie possible clinical effects of the vaccine. Both Epitope analysis of patients' immune responses will be carried out to identify GA733 antigen (Ag) fragments that may prove superior vaccine compared to the full-length Ag in future studies. To evaluate humoral immune responses in Ad-GA733-2 immunized CRC patients, induced antibodies will be tested for binding to GA733 Ag, Ag- positive tumor cells, cytotoxic reactivities against Ag-positive tumor cells and epitope specificity (using fragments of the GA733 Ag derived from Project 1). To evaluate T helper cell induction in Ad GA733-2 immunized patients, proliferative lymphocyte responses to the GA733 Ag will be demonstrated, followed by functional and phenotypic analysis of the proliferating cells. To evaluate cytotoxic T lymphocyte (CTL) responses in the vaccinated patients, CTL directed to the GA733 Ag will be identified. As an important correlate to the studies in CRC patients, the immune responses to the GA733 Ag- binding antibodies in approximately 50% of healthy individuals. Knowledge of the Ag-specificity and etiology of these immune responses is of utmost importance for the understanding of the mechanism(s) of immune response induction in CRC patients vaccinated with AdGA733-2. The proposed studies will determine the immunogenicity and mechanism of action of one of the best-studied CRC-associated Ags in patients. The identification of immunogenic epitopes/fragments of the GA733 Ag will provide new, potentially improved immunotherapies for CRC.