利用病毒感染/疫苗接种将高亲和性T细胞群集中到瘤中,使用瘤性病毒免疫疗法
Alexa Veliz Rios1, Muriel Metko1, Jason Tonne1
1Department of Molecular Medicine, Mayo Clinic, Rochester, MN 55905, USA.
概括
通过重定向先前存在的抗病毒T细胞反应,可以增强癌症免疫疗法. 这项研究表明使用SARS-CoV-2抗原与瘤病毒或CAR-T细胞将T细胞集中在瘤上,从而导致瘤治愈.
科学领域:
- 免疫学
- 癌症学
- 病毒学
背景情况:
- 免疫耐受性限制了T细胞对自身瘤相关抗原 (TAA) 的反应,阻碍了癌症免疫治疗.
- 病毒感染主要是高亲和性T细胞, 提供一种克服这种局限性的潜在策略.
研究的目的:
- 研究使用已存在的抗病毒T细胞记忆对抗SARS-CoV-2抗原以增强抗瘤免疫力.
- 探索瘤解毒病毒 (OV) 和虚拟抗原受体 (CAR) -T细胞传递病毒抗原以向瘤.
主要方法:
- 使用SARS-CoV-2抗原 (Mem或Spike蛋白) 的异质原始和OV/提升策略.
- 提供SARS-CoV-2抗原表达载体的化学抗原受体 (CAR) - T细胞疗法.
- 在体内用S蛋白疫苗增强S特异性CAR- T细胞.
主要成果:
- 使用T细胞聚焦的SARS-CoV-2抗原实现了CD8+T细胞依赖性瘤治愈,证据表明表位扩散对抗TAA.
- 即使在免疫前的小鼠中,CAR-T细胞也成功将SARS-CoV-2抗原载体输送到瘤中.
- 在体内增强CAR- T细胞增强了抗瘤活性和持久性.
结论:
- 通过OV或CAR-T细胞传递病毒抗原来利用先前存在的抗病毒T细胞反应是产生高亲和性T细胞用于癌症免疫治疗的可行策略.
- 这种方法提供了当高亲和力抗瘤T细胞不易获得时的治疗替代方案.
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