Phase 1 Study of Resiquimod Gel Therapy for Cutaneous T-Cell Lymphoma

瑞西莫德凝胶治疗皮肤 T 细胞淋巴瘤的 1 期研究

• 批准号: 8351030
• 负责人: JOEL M GELFAND
• 金额: $ 19.83万
• 依托单位: UNIVERSITY OF PENNSYLVANIA
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-09-01 至 2014-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8351030
• 关键词: Phase; Study; Resiquimod; Gel; Therapy

DESCRIPTION (provided by applicant): Cutaneous T-cell lymphoma (CTCL) is a rare malignancy of skin-trafficking CD4+ T-cells. Patients with advanced disease with extensive skin and blood involvement have a poor prognosis and exhibit marked defects in cell mediated immunity. Underlying these defects is an associated profound decline in the numbers of peripheral blood dendritic cells (DCs) along with marked deficiencies in the ability of these cells to produce cytokines, including interleukin-12 (I-12) and interferon alpha (IFN alpha), which are critical for antitumor immunity. Because host immune function appears to play an integral role in mediating disease-controlling responses in CTCL, the investigators have been investigating a number of mechanisms for activating DCs in patients, including the use of resiquimod which has been recognized as powerfully immune stimulatory by virtue of activation of DCs following binding to Toll like receptors (TLR) 7 and 8. Preliminary data of the investigators indicate that resiquimod exhibits the capacity to induce in vitro the production of high levels of the immune stimulatory cytokines interleukin-12 (IL-12) and interferon (IFN) alpha from the peripheral blood cells of advanced CTCL patients which is associated with marked activation of natural killer (NK) cells and cluster of differentiation (CD) 8+ T-cells and upregulation of CD80/CD86 on apoptotic cells (APCs). This grant proposes an initial single center phase 1, open label trial of resiquimod gel which is highly bioavailable through the skin. Patients with CTCL will be monitored for 1) clinical responses, 2) adverse effects, and a unique series of in vivo immunological assays including 3) in vivo immune stimulatory effects including DC, NK and CD8 T-cell activation, and cutaneous intralesional infiltration with CD8+ cytotoxic T-cells and NK cells as well as their ability to produce IFN gamma.

描述（由申请人提供）： 皮肤T细胞淋巴瘤（CTCL）是贩运CD4+ T细胞的罕见恶性肿瘤。具有广泛皮肤和血液参与的晚期疾病患者的预后较差，并且在细胞介导的免疫力中表现出明显的缺陷。这些缺陷的潜在缺陷是外周血树突状细胞（DC）的数量以及这些细胞产生细胞因子的能力的明显缺陷的巨大下降，包括白介素12（i-12）和胞介素α（IFN Alpha）（IFN Alpha），这对于抗抑制剂免疫至关重要。 Because host immune function appears to play an integral role in mediating disease-controlling responses in CTCL, the investigators have been investigating a number of mechanisms for activating DCs in patients, including the use of resiquimod which has been recognized as powerfully immune stimulatory by virtue of activation of DCs following binding to Toll like receptors (TLR) 7 and 8. Preliminary data of the investigators indicate that resiquimod exhibits从高级CTCL患者的周围血细胞中诱导高水平的免疫刺激细胞因子介导高水平的刺激细胞因子的能力，这些能力与自然杀伤（NK）细胞的显着激活（CD）8+ T-Cells cd86/cd86 cd86 cd86 cd86 cd86 cd86 cd86 cd86。该赠款提出了初始的单一中心阶段，即Resiquimod凝胶的开放标签试验，该试验在皮肤中非常有生物利用。将监测患有CTCL的患者1）临床反应，2）不良反应，以及一系列独特的体内免疫学测定法，包括3）体内免疫刺激作用，包括DC，NK和CD8 T细胞激活，以及皮肤透露型的cd8+ Cytototoxic T-CellS和NK细胞以及它们的能力以及IFN的能力。