内源性病毒元素构成了针对个性化癌症疫苗的抗原的补充来源
Christian Garde1, Michail A Pavlidis2, Pablo Garces2
1Evaxion Biotech A/S, Dr Neergaards Vej 5F, Hørsholm, Denmark. cg@evaxion.ai.
NPJ vaccines
|March 21, 2025
概括
个性化癌症疫苗 (PCV) 现在可以针对体内突变以外的内源逆转录病毒元素 (EVE). 这种方法有望改善癌症疫苗,特别是在低瘤突变负担 (TMB) 的患者中.
科学领域:
- 免疫学 免疫学 免疫学
- 在瘤学瘤学.
- 生物信息学是一种生物信息学.
背景情况:
- 目前的个性化癌症疫苗 (PCV) 主要依赖于体质突变的新抗原,限制了低瘤突变负担 (TMB) 癌症的疗效.
- 迫切需要替代性瘤抗原,以扩大PCVs的适用性,使其适用于更广泛的患者群体,包括低TMB患者.
- 内源逆转录病毒元素 (EVE) 代表了瘤相关抗原的尚未开发的来源.
研究的目的:
- 调查内源逆转录病毒元素 (EVE) 作为瘤抗原的潜力,以开发个性化癌症疫苗.
- 开发和验证一个计算管道,用于预测具有治疗潜力的EVE衍生表位.
- 在临床前模型中评估基于EVE的疫苗策略的免疫性和治疗疗效.
主要方法:
- 在健康组织和各种固体癌症中对EVE表达的大规模基因组分析.
- 在接受检查点抑制剂治疗的黑色素瘤患者中,EVE表达幅度和临床结果 (总生存率,无进展生存率) 之间的相关性分析.
- 开发ObsERV计算管道,用于预测瘤上呈现的EVE衍生的表位.
- 基于EVE的疫苗策略的临床前测试,以评估T细胞反应和瘤保护.
主要成果:
- 基因组分析证实了EVE作为多种癌症类型中普遍存在的瘤抗原.
- 瘤中EVE表达的幅度显著分层黑色素瘤患者,预测对检查点抑制剂治疗的不同反应.
- 该ObsERV管道成功预测了以EVE衍生的,作为瘤上的表位.
- 临床前研究表明,基于EVE的疫苗诱导了强大的多功能CD4+和CD8+T细胞反应,并提供了长期的瘤保护.
结论:
- 内源逆转录病毒元素 (EVE) 是个性化癌症疫苗瘤抗原的可行和有前途的来源.
- 该ObsERV计算管道为识别和设计基于EVE的候选疫苗提供了有价值的工具.
- 针对EVE的个性化癌症疫苗具有显著的潜力,可以改善治疗结果,特别是在低瘤突变负担 (TMB) 癌症患者中.
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