肿瘤细胞治疗研究
英文原题：Modern Advances in CARs Therapy and Creating a New Approach to Future Treatment.
Modern Advances in CARs Therapy and Creating a New Approach to Future Treatment.
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表达嵌合抗原受体（CAR）的基因工程T细胞和NK细胞，是治疗血液系统恶性肿瘤及实体瘤的有前景细胞。尽管CAR-T 细胞治疗已取得成功，但仍有细胞因子释放综合征（CRS）、神经毒性或移植物抗宿主病（GVHD）等缺点。CAR NK细胞引发的CRS和神经毒性较少或较轻，同时具有多种细胞毒作用机制。NK细胞适合开发可现成使用的治疗产品，且几乎不会引起移植物抗宿主病（GvHD），但更容易发生凋亡，基因表达水平也低于CAR-T 细胞。为避免这些不良反应，还需进一步改进，以提高过继细胞免疫疗法的有效性。一种有前景的策略是克服T细胞终末分化、衰老和耗竭。对此，免疫细胞来源的细胞外囊泡（EV）与药物联合治疗可能适用于癌症患者，尤其是兼具来源细胞细胞毒活性的效应T细胞和NK细胞来源外泌体。
Genetically engineered T and NK cells expressing a chimeric antigen receptor (CAR) are promising cytotoxic cells for the treatment of hematological malignancies and solid tumors. Despite the successful therapies using CAR-T cells, they have some disadvantages, such as cytokine release syndrome (CRS), neurotoxicity, or graft-versus-host-disease (GVHD). CAR-NK cells have lack or minimal cytokine release syndrome and neurotoxicity, but also multiple mechanisms of cytotoxic activity. NK cells are suitable for developing an "off the shelf" therapeutic product that causes little or no graft versus host disease (GvHD), but they are more sensitive to apoptosis and have low levels of gene expression compared to CAR-T cells.
To avoid these adverse effects, further developments need to be considered to enhance the effectiveness of adoptive cellular immunotherapy. A promising approach to enhance the effectiveness of adoptive cellular immunotherapy is overcoming terminal differentiation or senescence and exhaustion of T cells. In this case, EVs derived from immune cells in combination therapy with drugs may be considered in the treatment of cancer patients, especially effector T and NK cells-derived exosomes with the cytotoxic activity of their original cells.
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