个性化RNA新抗原疫苗刺激胰腺癌中的T细胞
Luis A Rojas1,2, Zachary Sethna1,2, Kevin C Soares2,3
1Immuno-Oncology Service, Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Nature
|May 10, 2023
概括
这项研究表明,与免疫疗法和化疗相结合的个性化新抗原疫苗 (自生菌) 可以刺激胰腺癌患者的T细胞反应. 这种T细胞活动可能有助于推迟手术后的癌症复发.
科学领域:
- 癌症学
- 免疫学
- 疫苗学
背景情况:
- 胰腺管腺癌 (PDAC) 的死亡率很高,88%的患者死于这种疾病.
- PDAC含有突变衍生新抗原,是疫苗治疗的潜在目标.
- 辅助疗法对于改善切除PDAC的结果至关重要.
研究的目的:
- 在PDAC的辅助环境中评估个性化mRNA新抗原疫苗的安全性和有效性.
- 评估疫苗诱导的T细胞反应及其与临床结果的相关性,包括无复发的存活率.
- 在PDAC患者中确定实时mRNA疫苗合成和施用的可行性.
主要方法:
- 一个I阶段试验,包括辅助性自体塞维梅兰,阿特佐利祖马布 (抗PD- L1) 和修改后的FOLFIRINOX化疗.
- 从手术切除的PDAC瘤中实时合成mRNA新抗原疫苗.
- 测量新抗原特异性T细胞反应的高值测试,T细胞追踪的CloneTrack测试和18个月无复发生存期的评估.
主要成果:
- 在16名患者中,8名患者接受了自生性塞武门,并诱导了新抗原特异性T细胞反应.
- 疫苗扩张的T细胞占血液T细胞的10%,经过强化剂的扩张,包括长寿命的CD8+T细胞.
- 与没有反应 (13. 4个月;P=0. 003) 相比,接种疫苗扩张的T细胞 (反应者) 的中位数无复发存活时间显著长 (未达到).
结论:
- 在PDAC患者中,辅助性阿特佐利祖马布,自发性塞维梅兰和mFOLFIRINOX联合治疗诱导显著的T细胞活性.
- 疫苗特异性T细胞反应的诱导与PDAC复发的延迟有关.
- 这种治疗策略作为辅助治疗有望改善切除PDAC的长期结果.
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