Survivin-specific T-cell reactivity correlates with tumor response and patient survival: a phase-II peptide vaccination trial in metastatic melanoma
Survivin-specific T-cell reactivity correlates with tumor response and patient survival: a phase-II peptide vaccination trial in metastatic melanoma
复制标题
DOI：
10.1007/s00262-012-1266-9
复制
发表时间：
2012-11-01
影响因子：
5.8
通讯作者：
Ugurel, Selma
中科院分区：
文献类型：
--
作者：
Becker, Juergen C.;Andersen, Mads H.;Ugurel, Selma
背景 旨在诱导抗肿瘤 T 细胞反应的治疗性疫苗接种是黑色素瘤治疗中广泛研究的领域。然而，许多黑色素瘤疫苗接种试验未能证明疫苗特异性免疫反应与治疗结果之间的相关性。这主要归因于抗原丢失导致的免疫逃逸，使我们需要新的疫苗接种靶点。 患者和方法 这项 II 期试验研究了针对 survivin 的肽疫苗接种，survivin 是一种对肿瘤细胞存活至关重要的致癌凋亡抑制剂蛋白，用于治疗难治性 IV 期转移性黑色素瘤的 HLA-A1/-A2/-B35 阳性患者。研究终点是生存素特异性 T 细胞反应性 (SSTR)、安全性、反应和生存 (OS)。 结果 61 名患者 (ITT) 使用三种不同的方案接受了疫苗接种治疗。 55 名患者 (PP) 可评估疗效和生存率，41/55 名患者可评估 SSTR。进展停滞 (CR + PR + SD) 的患者比疾病进展的患者更常表现出 SSTR (p = 0.0008)。接受 SSTR 的患者显示 OS 延长（中位 19.6 个月与 8.6 个月；p = 0.0077）；多变量分析证明 SSTR 是生存的独立预测因子 (p = 0.013)。 SSTR 的诱导与性别（女性与男性；p = 0.014）和疾病阶段（M1a/b 与 M1c；p = 0.010）相关，但与患者年龄、HLA 类型、体能状态或疫苗接种方案无关。 结论 Survivin 特异性 T 细胞反应性与肿瘤反应和患者存活率密切相关，表明使用 survivin 衍生肽进行疫苗接种是黑色素瘤的一种有前途的治疗策略。
Background Therapeutic vaccination directed to induce an anti-tumoral T-cell response is a field of extensive investigation in the treatment of melanoma. However, many vaccination trials in melanoma failed to demonstrate a correlation between the vaccine-specific immune response and therapy outcome. This has been mainly attributed to immune escape by antigen loss, rendering us in the need of new vaccination targets.Patients and methods This phase-II trial investigated a peptide vaccination against survivin, an oncogenic inhibitor-of-apoptosis protein crucial for the survival of tumor cells, in HLA-A1/-A2/-B35-positive patients with treatment-refractory stage-IV metastatic melanoma. The study endpoints were survivin-specific T-cell reactivity (SSTR), safety, response, and survival (OS).Results Sixty-one patients (ITT) received vaccination therapy using three different regimens. 55 patients (PP) were evaluable for response and survival, and 41/55 for SSTR. Patients achieving progression arrest (CR + PR + SD) more often showed SSTRs than patients with disease progression (p = 0.0008). Patients presenting SSTRs revealed a prolonged OS (median 19.6 vs. 8.6 months; p = 0.0077); multivariate analysis demonstrated SSTR as an independent predictor of survival (p = 0.013). The induction of SSTRs was associated with gender (female vs. male; p = 0.014) and disease stage (M1a/b vs. M1c; p = 0.010), but not with patient age, HLA type, performance status, or vaccination regimen.Conclusion Survivin-specific T-cell reactivities strongly correlate with tumor response and patient survival, indicating that vaccination with survivin-derived peptides is a promising treatment strategy in melanoma.