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）是一种罕见的皮肤恶性肿瘤运输CD 4 + T细胞。具有广泛皮肤和血液受累的晚期疾病的患者具有不良预后并且表现出细胞介导的免疫的显著缺陷。这些缺陷的潜在原因是外周血树突状细胞（DC）数量的严重下降，以及这些细胞产生细胞因子（包括白细胞介素-12（I-12）和干扰素α（IFN α））的能力的显着缺陷，这些细胞因子对于抗肿瘤免疫至关重要。沿着。由于宿主免疫功能似乎在介导CTCL中的疾病控制应答中起着不可或缺的作用，因此研究人员一直在研究用于激活患者中的DC的许多机制，包括使用瑞喹莫特，瑞喹莫特已被认为是由于在结合Toll样受体（TLR）7和8后激活DC而具有强大的免疫刺激性。研究者的初步数据表明，瑞喹莫特表现出在体外诱导晚期CTCL患者的外周血细胞产生高水平的免疫刺激细胞因子白介素-12（IL-12）和干扰素（IFN）α的能力，这与自然杀伤（NK）细胞和分化簇（CD）8+ T细胞的显著活化以及CD 80/CD 84 + T细胞的上调有关。凋亡细胞（APC）上的CD 86。该基金建议对瑞喹莫特凝胶进行初始单中心、1期、开放标签试验，瑞喹莫特凝胶通过皮肤具有高度生物利用度。将监测CTCL患者的1）临床反应，2）不良反应和一系列独特的体内免疫学试验，包括3）体内免疫刺激作用，包括DC、NK和CD 8 T细胞活化，以及CD 8+细胞毒性T细胞和NK细胞的皮肤病灶内浸润以及产生IFN γ的能力。