通过蛋白质工程空间时间编程细胞因子免疫疗法
Luciano Santollani1,2, K Dane Wittrup1,2
1Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA.
Immunological reviews
|July 6, 2023
概括
蛋白质工程通过控制其时间和位置来增强细胞因子免疫疗法,克服早期治疗的局限性. 这种方法旨在模仿自然的细胞因子功能,以提高癌症治疗效率.
科学领域:
- 免疫学 免疫学 免疫学
- 在瘤学瘤学.
- 蛋白质工程是指蛋白质的工程.
背景情况:
- 诸如INTERLEUKIN-2 (IL-2) 和INTERFERON-ɑ (IFNɑ) 这样的细胞因子在癌症免疫疗法中表现有前途,但临床成功有限.
- 早期的细胞因子疗法因治疗窗口狭窄和全身管理的剂量限制毒性而面临挑战.
- 局部化,受调节的内源性细胞因子作用与外源性疗法的全身性,非向性输送形成鲜明对比.
研究的目的:
- 探索蛋白质工程策略,以改善基于细胞因子的癌症免疫疗法.
- 通过先进的蛋白质设计来解决第一代细胞因子疗法的局限性.
- 通过时空调节来对细胞因子工程进行上下文化,以提高治疗潜力.
主要方法:
- 对细胞因子的蛋白质工程策略的审查和语境化.
- 专注于一些策略,如部分激应,条件激活和内保留.
- 通过太空时间调节细胞因子信号传递的透镜进行分析.
主要成果:
- 蛋白质工程提供解决方案,以克服狭窄的治疗窗口和剂量限制毒性.
- 诸如部分激应和条件激活等策略使控制的细胞因子信号传递成为可能.
- 内保留可以改善局部输送和治疗效果.
结论:
- 蛋白质工程可以使外源性细胞因子疗法更紧密地模仿内源性配置文件.
- 控制细胞因子信号的时间,地点,特异性和持续时间是关键.
- 这些进展使我们更接近于释放细胞因子在癌症治疗中的全部治疗潜力.
相关概念视频
01:29Microorganisms in Medicine and Therapeutics
64
Microorganisms play a fundamental role in vaccine development, gene therapy, and therapeutic production. Their biological properties are harnessed to advance medicine and public health. Beyond immunization, microorganisms contribute to gut health, antibiotic synthesis, and genetic disease treatment.Live Attenuated and Inactivated VaccinesLive attenuated vaccines, such as the measles, mumps, and rubella (MMR) vaccine, utilize weakened forms of pathogens to closely resemble natural infections.
64
01:27Tumor Immunotherapy
573
Immunotherapy is a treatment that boosts or manipulates the immune system to fight diseases, including cancer. For instance, by stimulating an immune response through vaccinations against viruses that cause cancers, like hepatitis B virus and human papillomavirus, these diseases can be prevented. Nonetheless, some cancer cells can avoid the immune system due to their rapid mutation and division. The immune response to many cancers involves three phases: elimination, equilibrium, and escape.
573