Adenovirus-mediated intralesional interferon-γ gene transfer induces tumor regressions in cutaneous lymphomas
Adenovirus-mediated intralesional interferon-γ gene transfer induces tumor regressions in cutaneous lymphomas
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DOI：
10.1182/blood-2004-01-0360
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发表时间：
2004-09-15
期刊：
影响因子：
20.3
通讯作者：
Urosevic, M
中科院分区：
文献类型：
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作者：
Dummer, R;Hassel, JC;Urosevic, M
原发性皮肤淋巴瘤已成功地治疗干扰素（IFN），平衡T辅助细胞2（Th 2）-偏斜状态。我们在晚期原发性皮肤T细胞淋巴瘤（CTCL）和多发性皮肤B细胞淋巴瘤（CBCL）患者中进行了一项1期、开放标签、剂量递增的重复肿瘤内给予TG 1042的试验。TG 1042是含有人IFN-γ cDNA插入片段的第三代非复制型人腺病毒载体。9例患者（7例CTCL，2例CBCL）以以下TG 1042剂量入组：3 x 10（9）、3 x 10（10）和3 x 10（11）总颗粒。在9例治疗患者中的5例中观察到局部临床应答（3例患者完全应答[CR]，2例患者部分应答[PR]）。其中，3例患者显示全身CR，其他非注射皮肤病变清除。临床缓解持续时间中位数为3个月（范围：1-6个月）。不良事件大多为1级和2级。在第一个治疗周期后，9名治疗患者中的7名在注射的病变中具有可检测的TG 1042衍生的IFN-γ信息。在几个治疗周期后也可检测到TG 1042 IFN-γ信息。我们证明了治疗后对淋巴瘤肿瘤抗原se 70 -2的体液免疫应答的诱导。我们的研究表明，病灶内注射TG 1042是安全的，耐受性良好。(C)2004年，美国血液学会。
Primary cutaneous lymphomas have been successfully treated with interferons (IFNs), counterbalancing the T-helper 2 (Th2)-skewing state. We undertook a phase 1, open-label, dose-escalating trial of repeated intratumoral administration of TG1042 in patients with advanced primary cutaneous T-cell lymphomas (CTCLs) and multilesional cutaneous B-cell lymphomas (CBCLs). TG1042 is a third-generation, non-replicating human adenovirus vector containing a human IFN-gamma cDNA insert. Nine patients (7 CTCL, 2 CBCL) were enrolled at the following TG1042 doses: 3 x 10(9), 3 x 10(10), and 3 x 10(11) total particles. Local clinical response was observed in 5 of 9 treated patients (3 patients with complete response [CR] and 2 patients with partial response [PR]). Out of these, 3 patients showed systemic CR with the clearance of other noninjected skin lesions. Clinical response lasted for a median of 3 months (range, 1-6 months). Adverse events were mostly of grades 1 and 2. Seven of 9 treated patients had a detectable TG1042- derived IFN-gamma message in injected lesions after the first treatment cycle. A TG 1042IFN-gamma message was also detectable after several treatment cycles. We demonstrate the induction of humoral immune response to lymphoma tumor-antigen se70-2 after treatment. Our study shows that intralesional injections of TG1042 are both safe and well tolerated. (C) 2004 by The American Society of Hematology.