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在HPV16+宫癌治疗后对HPV16 L2E7E6融合蛋白接种部位进行随机试验

Stéphanie Gaillard¹, Jade Alvarez², Tianbei Zhang³

¹Department of Oncology, Johns Hopkins School of Medicine; Baltimore, MD, USA; Department of Gynecology/Obstetrics, Johns Hopkins School of Medicine; Baltimore, MD, USA.

Gynecologic oncology

|August 21, 2025

概括

与手臂疫苗接种相比,用TA- CIN (HPV16 L2E7E6融合蛋白) 接种大腿疫苗对宫癌患者产生了更强的免疫反应,包括更高的抗体和CD8 T细胞活性. 在没有疾病迹象的患者中,这种方法是安全的,并且耐受良好.

科学领域:

免疫学
癌症学
疫苗学

背景情况:

在临床前模型中,通过疫苗接种策略可以增强抗瘤免疫力.
人类乳头瘤病毒16型 (HPV16) 是宫癌的主要致癌因素.
HPV16 L2E7E6融合蛋白 (TA-CIN) 是一个候选治疗疫苗.

研究的目的:

在HPV16+宫癌患者中,比较TA- CIN在大腿和手臂中的免疫性.
评估TA-CIN疫苗接种在初级治疗后没有疾病迹象的患者的安全性和有效性.

主要方法:

一项试点研究随机选择了15名没有疾病迹象的HPV16+宫癌患者,每月在手臂或大腿接受三次肌内TA- CIN免疫接种 (100微克).
使用CTCAEv4. 0标准评估安全性,并通过抗体标位,批量T细胞受体测序 (TCRseq) 和单细胞RNA测序 (scRNAseq) 分析免疫反应.
对患者进行了两年的复发跟踪.

主要成果:

TA-CIN疫苗接种耐受性良好,主要是注射部位发生1级治疗相关的不良事件.
与手臂疫苗接种相比,大腿疫苗接种导致TA- CIN特异性抗体标位更高,T细胞克隆扩张明显更大 (包括E6,E7和L2特异性).
在接种疫苗后,scRNAseq发现了MAIT和细胞毒性CD8+T细胞的显著扩张,主要是L2特异性T细胞反应和新型TCR克隆型.

结论:

在没有疾病迹象的HPV16+宫癌患者中,肌肉内TA- CIN疫苗接种是安全的,并引起强烈的免疫反应.
与手臂接种疫苗相比,大腿接种疫苗表现出优异的免疫性,诱导更高的CD8T细胞和抗体反应.
作为HPV16驱动癌症的治疗策略,TA- CIN疫苗需要进一步研究.

关键词:

宫癌没有.美国在HPV16 一个L2 免疫疗法

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