Phase II Trial of Nelipepimut-S Peptide Vaccine in Women with Ductal Carcinoma In Situ.
Phase II Trial of Nelipepimut-S Peptide Vaccine in Women with Ductal Carcinoma In Situ.
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Nelipepimut-S 肽疫苗治疗导管原位癌女性的 II 期试验。
DOI：
10.1158/1940-6207.capr-22-0388
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发表时间：
2023
期刊：
影响因子：
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通讯作者：
Vornik,La
中科院分区：
文献类型：
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作者：
O'Shea,AnneE;Clifton,GuyT;Qiao,Na;Heckman-Stoddard,BrandyM;Wojtowicz,Malgorzata;Dimond,Eileen;Bedrosian,Isabelle;Weber,Diane;Garber,JudyE;Husband,Alexander;Pastorello,Ricardo;Lee,JJack;Hernandez,Mike;Liu,DianeD;Vornik,La
NeuVax 是一种由 HER2 衍生的 MHC I 类肽 E75（nelipepimut-S，NPS）与 GM-CSF 组合而成的疫苗。我们在导管原位癌 (DCIS) 患者中完成了一项术前接种 NeuVax 与单独接种 GM-CSF 的随机试验。主要目的是评估 NPS 特异性细胞毒性 T 淋巴细胞 (CTL) 反应。人类白细胞抗原 (HLA)-A2 阳性 DCIS 患者被纳入并以 2:1 的比例随机分配至 NeuVax 组与单独 GM-CSF 组，并在手术前接受两次接种。通过右旋聚体测定在疫苗接种前、手术时以及术后1个月和3至6个月测量NPS特异性CTL的数量。使用双样本检验或 Wilcoxon 秩和检验分析组间以及疫苗接种前和术后 1 个月之间 CTL 反应的差异。比较各组之间不良事件的发生率和严重程度。总共登记了 45 名患者； 20 名患者 HLA-A2 阴性，7 名拒绝参加，1 名退出，4 名因其他原因未能筛查。其余 13 名患者被随机分配接受 NeuVax (n= 9) 或单独接受 GM-CSF (n= 4)。疫苗接种耐受性良好，各组之间的治疗相关毒性相似，大多数 (>89%) 不良事件为 1 级。从基线（疫苗接种前）到术后 1 个月，两组中 NPS 特异性 CTL 的百分比均有所增加。 NPS+GM-CSF 组的增加在数值上更大，但差异不具有统计学意义。 DCIS 患者术前给予 NPS+GM-CSF 是安全且耐受性良好的。在 HLA-A2 阳性 DCIS 患者中，两次接种 NPS+GM-CSF 可以诱导体内免疫和术后 1 个月持续的抗原特异性 T 细胞应答。预防相关性本试验表明，在术前为 HLA-A2 阳性 DCIS 患者接种 NeuVax 疫苗可以诱导持续的抗原特异性 T 细胞应答。这提供了原理证明，即术前或辅助接种疫苗可能会刺激适应性免疫反应，从而有可能预防疾病复发。
NeuVax is a vaccine comprised of the HER2-derived MHC class I peptide E75 (nelipepimut-S, NPS) combined with GM-CSF. We completed a randomized trial of preoperative vaccination with NeuVax versus GM-CSF alone in patients with ductal carcinomain situ(DCIS). The primary objective was to evaluate for NPS-specific cytotoxic T lymphocyte (CTL) responses. Patients with human leukocyte antigen (HLA)-A2-positive DCIS were enrolled and randomized 2:1 to NeuVax versus GM-CSF alone and received two inoculations prior to surgery. The number of NPS-specific CTL was measured pre-vaccination, at surgery, and 1 and 3 to 6 months post-operation by dextramer assay. Differences in CTL responses between groups and between pre-vaccination and 1-month post-operation were analyzed using a two-samplettest or Wilcoxon rank sum test. The incidence and severity of adverse events were compared between groups. Overall, 45 patients were registered; 20 patients were HLA-A2 negative, 7 declined participation, 1 withdrew, and 4 failed screening for other reasons. The remaining 13 were randomized to NeuVax (n= 9) or GM-CSF alone (n= 4). Vaccination was well-tolerated with similar treatment-related toxicity between groups with the majority (>89%) of adverse events being grade 1. The percentage of NPS-specific CTLs increased in both arms between baseline (pre-vaccination) and 1-month post-operation. The increase was numerically greater in the NPS+GM-CSF arm, but the difference was not statistically significant. NPS+GM-CSF is safe and well-tolerated when given preoperatively to patients with DCIS. In patients with HLA-A2-positive DCIS, two inoculations with NPS+GM-CSF can inducein vivoimmunity and a continued antigen-specific T-cell response 1-month postsurgery.Prevention RelevanceThis trial showed that vaccination of patients with HLA-A2-positive DCIS with NeuVax in the preoperative setting can induce a sustained antigen-specific T-cell response. This provides proof of principle that vaccination in the preoperative or adjuvant setting may stimulate an adaptive immune response that could potentially prevent disease recurrence.