PATIENTS' IMMUNE RESPONSES

拟议研究的主要目标是评估幽默和 结直肠癌患者的细胞免疫应答 重组腺病毒疫苗接种(在项目3中) CRC相关抗原GA733(AdGA733-2)。对接种疫苗的评价 患者对AdGA733-2的免疫反应将使我们深入了解 免疫机制(S)，可能是可能的临床效果的基础 疫苗。对患者免疫反应的表位分析将是 用来鉴定GA733抗原(Ag)片段可能证明 在未来的研究中，疫苗比全长的Ag更优越。 Ad-GA733-2免疫结直肠癌的体液免疫应答 患者，将测试诱导抗体与GA733 Ag，Ag- 阳性肿瘤细胞，对Ag阳性肿瘤的细胞毒反应 细胞和表位特异性(使用来自GA733 Ag的片段 来自项目1)。Ad GA733-2对辅助性T细胞的诱导作用 免疫病人对GA733抗原的增殖性淋巴细胞反应 将进行演示，然后进行功能和表型分析 正在增殖的细胞。细胞毒性T淋巴细胞(CTL)的检测 在接种疫苗的患者中，针对GA733抗原的CTL将被 已确认身份。 作为结直肠癌患者研究的一个重要相关性，免疫 大约50%的人对GA733抗原结合抗体的反应 健康的个体。对这些疾病的抗原特异性和病因学的认识 免疫反应对于了解人类免疫功能至关重要。 结直肠癌患者接种卡介苗诱导免疫应答的机制(S) AdGA733-2。 拟议的研究将确定其免疫原性和机制。 研究最多的结直肠癌相关AGS之一在患者中的作用。这个 GA733抗原遗嘱免疫原性表位/片段的鉴定 为结直肠癌提供新的、可能得到改进的免疫疗法。

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.