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在癌症免疫学和免疫治疗中使用介质素-18
Assunta Cirella1,2, Irene Olivera1,2, Carlos Luri-Rey1,2
1Program of Immunology and Immunotherapy, Cima Universidad de Navarra, Pamplona, Spain.
Expert opinion on therapeutic targets
|November 22, 2023
概括
介质素-18 (IL-18) 在癌症免疫疗法中表现有前途,特别是在与其他治疗相结合或局部输送时. 新型IL-18变种抵抗抑制,增强抗瘤效果,用于潜在的治疗应用.
科学领域:
- 免疫学 免疫学 免疫学
- 在瘤学瘤学.
- 分子生物学分子生物学
背景情况:
- 介素-18 (IL-18) 是一种炎症调解剂,可以刺激免疫细胞的IFNγ分泌.
- 在癌症免疫治疗中IL-18的治疗潜力受到适度的抗瘤活性和IL-18结合蛋白 (IL-18BP) 的下调限制.
研究的目的:
- 探索新型IL-18结构和癌症治疗组合疗法的疗效.
- 为了研究mRNA联合递送在局部IL-18和IL-12的潜力.
主要方法:
- 开发了对IL-18BP有抗性的IL-18结构.
- 在小鼠模型中使用mRNA内共递的IL-18和IL-12联合治疗的临床前评估.
- 工程T细胞具有编码IL-18和IL-12的mRNA.
主要成果:
- 不结合IL-18BP的IL-18结构显示出增加的抗瘤作用.
- 在小鼠模型中,通过mRNA对IL-12和诱抗性IL-18的内联合递送显示出有效性.
- 用编码IL-18和IL-12的mRNA对T细胞进行过渡工程,实现了协同作用的抗瘤效应.
结论:
- IL-18对癌症免疫疗法具有显著的前景,特别是在组合策略和局部递送方法中.
- 抗诱的IL-18变种和基于mRNA的局部输送代表了提高癌症治疗疗效的有希望的途径.
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