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（申请人提供）：大多数卵巢癌患者在诊断时已处于晚期疾病，卵巢癌是妇科恶性肿瘤中死亡率最高的。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是这些患者的可行治疗方法。近年来，癌症免疫治疗的前景急剧上升，部分基于对可作为 CTL 靶标的肿瘤特异性抗原的共同努力，部分基于树突状细胞 (DC) 作为肿瘤强大诱导剂的应用-特异性T细胞反应。 DCV Technologies 将利用一系列新型卵巢肿瘤抗原的鉴定，特别是角质层糜蛋白酶 (SCCE)，来开发卵巢癌治疗性 DC 疫苗。 SCCE 在卵巢癌中高表达，但在正常卵巢或其他正常成人组织中不表达。用 SCCE 肽脉冲的 DC 可以刺激 CD4+ 辅助 T 细胞反应和 HLA A2.1 限制性 CD8+ CTL，从而杀死 A2.1 匹配的卵巢肿瘤细胞。第一个具体目标将进一步鉴定具有刺激 SCCE 特异性 CD4+ T 细胞反应能力的 25-30 个残基肽。在第二个具体目标中，我们将确定负载延伸肽的 DC 是否也能够交叉引发 SCCE 特异性 CD8+ CTL 反应。这一策略的基本原理是，抗原特异性 CD4+ T 细胞为诱导有效的 CD8+ T 细胞反应提供了必要的帮助，无论是在支持方面。 DC 成熟并支持抗原特异性 CD8+ T 细胞在体内的持续存在。能够诱导 CD8+ CTL 反应和 CD4+ 辅助 T 细胞反应的肽负载 DC 免疫疗法因此比单独使用负载 CD8+ CTL 肽表位的 DC 治疗提供了更大的诱导持久免疫反应和临床益处的潜力。该项目旨在支持开发卵巢癌患者治疗性 DC 疫苗接种的临床试验方案。