CAR-T(CAR-T)细胞疗法在非肿瘤性疾病中的应用
Chimeric antigen receptor T (CAR-T) cell therapy in non-oncological diseases.
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:Lck Function and Modulation: Immune Cytotoxic Response and Tumor Treatment More Than a Simple Event.
Lck Function and Modulation: Immune Cytotoxic Response and Tumor Treatment More Than a Simple Event.
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Lck 是 Src 激酶家族的一员,是一种非受体酪氨酸激酶,参与免疫细胞活化、抗原识别、肿瘤生长和细胞毒性反应。该酶通常与抗原识别后的 T 淋巴细胞活化相关。Lck 的激活对 CD4、CD8 和 NK 细胞的活化至关重要。
然而,近来更清楚地表明,在 CD8 细胞中激活该酶可以不依赖于抗原呈递,并增强细胞毒性反应。Lck 在 NK 细胞毒性功能中的作用一直存在争议,其方式与该酶在 CAR-T 细胞中的作用类似。抑制酪氨酸激酶一直是治疗血液系统恶性肿瘤非常成功的方法。这些抑制剂可能可用于治疗其他肿瘤类型,也可能有助于防止细胞耗竭。已有新的、更具选择性的抑制剂被报道,它们不仅在肿瘤生长方面,也在自身免疫性疾病、哮喘和移植物抗宿主病的治疗中显示出令人关注的活性。药物重定位和生物信息学有助于解决关于 Lck 在癌症中作用的若干未解问题。
总之,Lck 在免疫反应和肿瘤生长中的作用并非单一事件,需要更多研究。
Lck, a member of the Src kinase family, is a non-receptor tyrosine kinase involved in immune cell activation, antigen recognition, tumor growth, and cytotoxic response. The enzyme has usually been linked to T lymphocyte activation upon antigen recognition. Lck activation is central to CD4, CD8, and NK activation.
However, recently, it has become clearer that activating the enzyme in CD8 cells can be independent of antigen presentation and enhance the cytotoxic response. The role of Lck in NK cytotoxic function has been controversial in a similar fashion as the role of the enzyme in CAR T cells. Inhibiting tyrosine kinases has been a highly successful approach to treating hematologic malignancies. The inhibitors may be useful in treating other tumor types, and they may be useful to prevent cell exhaustion.
New, more selective inhibitors have been documented, and they have shown interesting activities not only in tumor growth but in the treatment of autoimmune diseases, asthma, and graft vs. host disease. Drug repurposing and bioinformatics can aid in solving several unsolved issues about the role of Lck in cancer. In summary, the role of Lck in immune response and tumor growth is not a simple event and requires more research.
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