共同的表位因而在一些癌症疫苗中引起了安全性和有效性的担忧
Guillaume Kellermann1, Baharia Mograbi2,3,4,5, Paul Hofman2,3,4,5,6
1Telomium, SAS, IVRY SUR SEINE, Île-de-France, France guikell@gmail.com.
Journal for immunotherapy of cancer
|July 11, 2025
概括
许多癌症疫苗向瘤相关抗原 (TAA),但与正常蛋白质共享的表位素可能会损害安全性和有效性. 下一代疫苗需要改进表位镜以获得更好的T细胞免疫力.
科学领域:
- 免疫学 免疫学 免疫学
- 在瘤学瘤学.
- 疫苗开发 疫苗开发
背景情况:
- 治疗性癌症疫苗的目标是瘤相关抗原 (TAA).
- TAA通常含有与正常人类蛋白质共享的表位,构成安全风险.
- 一些TAA在瘤中表达较低,而在健康组织中表达较低.
研究的目的:
- 评估当前治疗癌症疫苗的设计.
- 为了确定潜在的安全性和有效性问题,源于共同的表征.
- 为下一代癌症疫苗开发提出改进建议.
主要方法:
- 分析瘤相关抗原 (TAA) 和它们的表位.
- 将TAA表位序列与人类蛋白质组进行比较.
- 在健康组织与瘤组织中评估非目标蛋白质表达水平.
主要成果:
- 在几个癌症疫苗中确定了TAA和正常蛋白质之间的共享表位.
- 与瘤特异性TAA相比,在健康组织中观察到非标蛋白的更高表达.
- 在ATP128,BNT111,BNT112,BNT116和INO-5401等癌症疫苗中突出显示了次优设计.
结论:
- 目前针对TAA的癌症疫苗设计可能具有亚最佳表位选择.
- 共享的表位可导致不良事件和治疗效率降低.
- 下一代癌症疫苗必须采用严格的表位过来提高安全性和有效性.
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