Dendritic cell immunotherapy for ovarian cancer

卵巢癌的树突状细胞免疫疗法

• 批准号: 6882806
• 负责人: Martin J Cannon
• 金额: $ 6.68万
• 依托单位: DCV TECHNOLOGIES, INC.
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-05-01 至 2007-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6882806
• 关键词: Dendritic; cell; immunotherapy; ovarian; cancer

DESCRIPTION (provided by applicant): The majority of ovarian cancer patients have advanced disease at the time of diagnosis, and ovarian cancer has the highest mortality rate among gynecological malignancies. Immunotherapy based on induction of tumor-specific cytotoxic T lymphocyte (CTL) responses may represent a viable treatment for these patients. The prospects for immunological treatment of cancer have risen sharply in recent years, based in part on concerted efforts to identify tumor-specific antigens that may serve as CTL targets, and in part on the application of dendritic cells (DC) as powerful inducers of tumor-specific T cell responses. DCV Technologies will exploit the identification of a series of novel ovarian tumor antigens, in particular stratum corneum chymotryptic enzyme (SCCE), for the development of therapeutic DC vaccines for ovarian cancer. SCCE is highly expressed in ovarian cancer, but not in normal ovaries or other normal adult tissues. DC pulsed with SCCE peptides can stimulate CD4+ helper T cell responses and HLA A2.1-restricted CD8+ CTL that kill A2.1-matched ovarian tumor cells. The 1st Specific Aim will identify further 25-30 residue peptides with the ability to stimulate SCCE-specific CD4+ T cell responses. In the 2nd Specific Aim, we will determine whether DC loaded with extended peptides are also capable of cross-priming SCCE-specific CD8+ CTL responses. The rationale for this strategy is that antigen-specific CD4+ T cells provide essential help for the induction of effective CD8+ T cell responses, both in terms of supporting. DC maturation and also for supporting the persistence of antigen-specific CD8+ T cells in vivo. Peptide-loaded DC immunotherapy that is capable of inducing both CD8+ CTL responses and CD4+ helper T cell responses thus offers greater potential for inducing durable immune responses and clinical benefit than treatment with DC loaded withCD8+ CTL peptide epitopes alone. This project is designed to support the development of clinical trial protocols for therapeutic DC vaccination in patients with ovarian cancer.

描述（由申请人提供）：大多数卵巢癌患者在诊断时患有晚期疾病，而卵巢癌的死亡率最高。基于诱导肿瘤特异性细胞毒性T淋巴细胞（CTL）反应的免疫疗法可能代表这些患者的可行治疗。近年来，癌症免疫治疗的前景急剧上升，部分基于鉴定可能充当CTL靶标的肿瘤特异性抗原的努力，部分是基于树突状细胞（DC）作为肿瘤特异性T细胞反应的强大诱导剂的应用。 DCV技术将利用一系列新型卵巢肿瘤抗原的鉴定，尤其是角质层角膜胰蛋白酶酶（SCCE），以开发用于卵巢癌的治疗性直流疫苗。 SCCE在卵巢癌中高度表达，但在正常卵巢或其他正常成年组织中不表达。用SCCE肽脉冲的直流可以刺激CD4+辅助T细胞反应和HLA A2.1限制的CD8+ CTL，从而杀死A2.1匹配的卵巢肿瘤细胞。第一个特定的目标将识别出具有刺激SCCE特异性CD4+ T细胞反应的能力的25-30个残基肽。在第二个特定目的中，我们将确定是否加载了带有扩展肽的直流也能够交叉染色SCCE特异性的CD8+ CTL响应。该策略的理由是，抗原特异性的CD4+ T细胞为诱导有效的CD8+ T细胞反应提供了必不可少的帮助。 DC成熟，还支持体内抗原特异性CD8+ T细胞的持久性。肽负载的DC免疫疗法能够同时诱导CD8+ CTL反应和CD4+辅助T细胞反应，因此与仅用CT8+ CTL肽表位的DC处理相比，与使用DC处理的治疗相比，具有更大的诱导耐用免疫反应和临床益处的潜力。该项目旨在支持卵巢癌患者治疗性直流疫苗的临床试验方案的开发。