Gaillard Stéphanie, Alvarez Jade, Zhang Tianbei, Wang Hao, Tsai Hua-Ling, Cope Leslie, Deery Amy, Palande Vikrant, Lee Chi-Fen, Fader Amanda N, Huh Warner K, Arend Rebecca C, Liang Margaret I, Straughn J Michael, Vang Russell, Ostrander Darin, Horner Karen, Zhang Li, Singh Dipika, Smith Kellie N, Wu T C, Leath Charles A, Roden Richard B S
Department of Oncology, Johns Hopkins School of Medicine; Baltimore, MD, USA; Department of Gynecology/Obstetrics, Johns Hopkins School of Medicine; Baltimore, MD, USA.
Department of Pathology, Johns Hopkins School of Medicine; Baltimore, MD, USA.
Gynecol Oncol. 2025 Aug 20;201:86-96. doi: 10.1016/j.ygyno.2025.08.006.
Since anti-tumor immunity is enhanced by vaccination of mice adjacent to human papillomavirus type 16 (HPV16+) tumors, we examined whether HPV16 L2E7E6 fusion protein (TA-CIN) vaccination in the thigh of HPV16+ cervical cancer patients would be more immunogenic than their arm.
HPV16+ cervical cancer (stage IB1-IVA) patients, who had completed standard-of-care treatment within the past year and absent evidence of disease (NED), were enrolled in a pilot study (NCT02405221). Participants were randomized 1:1 to receive three 100 μg TA-CIN monthly intramuscular immunizations either in the arm or thigh and followed for two years for safety (CTCAEv4.0), immune response, and recurrence.
Fifteen patients were enrolled (median age 44, range 35-83 years); one patient experienced a non-vaccine-related adverse event after one vaccination and withdrew. Treatment-related adverse events (n = 8) were grade 1, primarily at the injection site, and self-resolved. No recurrence was observed. TA-CIN-specific antibody titers tended to be higher in thigh-vaccinated patients. Bulk TCRseq revealed significant increases in expanded and de novo T cell clones following thigh-vaccination compared with the arm. No correlation with prior treatment modality was observed. E6-, E7-, and L2-specific TCR clones expanded, although L2-specific T cell responses were predominant. One month post-vaccination, scRNAseq revealed significant expansion of MAIT and cytotoxic CD8+ T cells, and both expanded and novel TCR clonotypes were identified in the latter.
Thigh or arm vaccination with TA-CIN was well tolerated, but the former elicited higher CD8 T cell and antibody responses in HPV16+ cervical cancer patients with NED after primary therapy.
由于对人乳头瘤病毒16型（HPV16+）肿瘤附近的小鼠进行疫苗接种可增强抗肿瘤免疫力，我们研究了在HPV16+宫颈癌患者大腿接种HPV16 L2E7E6融合蛋白（TA-CIN）疫苗是否比在手臂接种更具免疫原性。
过去一年内完成标准治疗且无疾病证据（NED）的HPV16+宫颈癌（IB1-IVA期）患者被纳入一项试点研究（NCT02405221）。参与者按1:1随机分组，每月在手臂或大腿进行三次100μg TA-CIN肌肉注射免疫，并随访两年以观察安全性（CTCAEv4.0）、免疫反应和复发情况。
共纳入15名患者（中位年龄44岁，范围35-83岁）；一名患者在一次接种后出现非疫苗相关不良事件并退出。与治疗相关的不良事件（n = 8）为1级，主要发生在注射部位，可自行缓解。未观察到复发情况。大腿接种患者的TA-CIN特异性抗体滴度往往更高。大量TCRseq分析显示，与手臂接种相比，大腿接种后扩增的和新生的T细胞克隆显著增加。未观察到与先前治疗方式的相关性。E6、E7和L2特异性TCR克隆均有扩增，尽管L2特异性T细胞反应占主导。接种疫苗后1个月，scRNAseq分析显示MAIT细胞和细胞毒性CD8+ T细胞显著扩增，且在后者中鉴定出扩增的和新的TCR克隆型。
TA-CIN在大腿或手臂接种耐受性良好，但在接受过初始治疗的HPV16+ NED宫颈癌患者中，前者引发的CD8 T细胞和抗体反应更高。
