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新抗原疫苗在细胞癌中产生抗瘤免疫力

David A Braun^1,2,3, Giorgia Moranzoni⁴, Vipheaviny Chea⁵

¹Section of Medical Oncology, Department of Internal Medicine, Yale School of Medicine, New Haven, CT, USA. david.braun@yale.edu.

|February 5, 2025

概括

针对新抗原的个性化癌症疫苗 (PCV) 在清细胞癌 (RCC) 患者中显示出高免疫性. 这种方法显示出作为有效辅助疗法的潜力,在研究队列中没有观察到复发.

科学领域:

癌症学
免疫学
疫苗开发

背景情况:

个性化癌症疫苗 (PCV) 旨在引起针对患者特定的新抗原的免疫反应.
针对癌症驱动突变和诱导临床活性,特别是低突变负担的瘤的PCV的能力仍然在很大程度上未被探索.
清细胞细胞癌 (RCC) 是一种严重的恶性瘤,需要新的辅助疗法.

研究的目的:

评估新抗原向PCV的安全性和免疫性,对患有高风险,切除的清细胞癌 (RCC) 的患者进行评估.
评估PCVs诱导T细胞对抗癌症驱动突变和自身瘤的潜力.
研究PCV作为RCC的辅助疗法的临床活性.

主要方法:

进行了一项I期临床试验 (NCT02950766),涉及9名高风险,完全切除RCC的参与者.
参与者接受了新抗原向PCV,有或没有ipilimumab,作为辅助治疗.
评估了免疫反应,包括T细胞对PCV抗原和自身瘤的反应,以及复发和毒性等临床结果.

主要成果:

在40. 2个月的中位随访期内,没有参与者出现RCC的复发.
所有患者都产生了针对PCV抗原的T细胞免疫反应,包括针对RCC驱动突变 (VHL,PBRM1,BAP1,KDM5C,PIK3CA).
观察到周围T细胞克隆的持续扩张,并且在9名患者中检测到7名T细胞对自身瘤的反应性. 没有报告剂量限制性毒性.

结论:

在高危RCC患者中,针对新抗原的PCV具有高度免疫性.
这些疫苗可以有效地向关键的癌症驱动突变并诱导抗瘤免疫力.
这些有前途的结果,包括没有复发,表明PCV具有作为RCC有效辅助治疗的潜力.

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