Given its ability to induce both humoral and cellular immune responses, NY-ESO-1 has been considered a suitable antigen for a cancer vaccine. Despite promising results from early-phase clinical studies in patients with melanoma, NY-ESO-1 vaccine immunotherapy has not been widely investigated in larger trials; consequently, many questions remain as to the optimal vaccine formulation, predictive biomarkers, and sequencing and timing of vaccines in melanoma treatment. We conducted an adjuvant phase I/II clinical trial in high-risk resected melanoma to optimize the delivery of poly-ICLC, a TLR-3/MDA-5 agonist, as a component of vaccine formulation. A phase I dose-escalation part was undertaken to identify the MTD of poly-ICLC administered in combination with NY-ESO-1 and montanide. This was followed by a randomized phase II part investigating the MTD of poly-ICLC with NY-ESO-1 with or without montanide. The vaccine regimens were generally well tolerated, with no treatment-related grade 3/4 adverse events. Both regimens induced integrated NY-ESO-1-specific CD4+ T-cell and humoral responses. CD8+ T-cell responses were mainly detected in patients receiving montanide. T-cell avidity toward NY-ESO-1 peptides was higher in patients vaccinated with montanide. In conclusion, NY-ESO-1 protein in combination with poly-ICLC is safe, well tolerated, and capable of inducing integrated antibody and CD4+ T-cell responses in most patients. Combination with montanide enhances antigen-specific T-cell avidity and CD8+ T-cell cross-priming in a fraction of patients, indicating that montanide contributes to the induction of specific CD8+ T-cell responses to NY-ESO-1.

中文翻译：

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NY-ESO-1 蛋白、Poly-ICLC 和 Montanide 联合疫苗接种可改善高危黑色素瘤患者的体液和细胞免疫反应。


鉴于其诱导体液和细胞免疫反应的能力，NY-ESO-1被认为是癌症疫苗的合适抗原。尽管黑色素瘤患者的早期临床研究取得了有希望的结果，但 NY-ESO-1 疫苗免疫疗法尚未在更大规模的试验中得到广泛研究；因此，关于黑色素瘤治疗中的最佳疫苗配方、预测性生物标志物以及疫苗的排序和时机仍然存在许多问题。我们在高风险切除黑色素瘤中进行了辅助 I/II 期临床试验，以优化作为疫苗配方成分的 TLR-3/MDA-5 激动剂 Poly-ICLC 的输送。进行 I 期剂量递增部分以确定与 NY-ESO-1 和 montanide 联合给药的聚 ICLC 的 MTD。接下来是随机 II 期部分，研究聚-ICLC 与 NY-ESO-1（有或没有 montanide）的 MTD。疫苗方案总体耐受性良好，没有出现与治疗相关的 3/4 级不良事件。两种方案均诱导整合的 NY-ESO-1 特异性 CD4+ T 细胞和体液反应。 CD8+ T 细胞反应主要在接受 montanid 的患者中检测到。接种 montanide 疫苗的患者中，T 细胞对 NY-ESO-1 肽的亲和力较高。总之，NY-ESO-1 蛋白与聚 ICLC 组合是安全的，耐受性良好，并且能够在大多数患者中诱导整合抗体和 CD4+ T 细胞反应。与 montanide 组合可增强部分患者的抗原特异性 T 细胞亲合力和 CD8+ T 细胞交叉引发，表明 montanide 有助于诱导对 NY-ESO-1 的特异性 CD8+ T 细胞反应。