肿瘤细胞治疗研究
英文原题:CRISPR/Cas9 Technology for Modifying Immune Checkpoint in CAR-T Cell Therapy for Hematopoietic Malignancies.
CRISPR/Cas9 Technology for Modifying Immune Checkpoint in CAR-T Cell Therapy for Hematopoietic Malignancies.
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血液系统恶性肿瘤源于造血调控失常,是一组起源于分化成熟能力下降细胞的癌症;未成熟细胞在淋巴结和骨髓等造血组织中积聚。免疫靶向疗法,如免疫检查点阻断(ICB)、CAR-T(CAR-T)细胞疗法,以及精准、常用且用途广泛的基因组工程工具CRISPR系统,为恶性肿瘤治疗开辟了新途径。靶向免疫检查点已推动细胞毒性T淋巴细胞相关蛋白4(CTLA-4)、PD-1(程序性死亡蛋白1)及PD-L1等靶点疗法获美国食品药品监督管理局批准。根据ICB及CAR技术原理,高效CAR-T 细胞的制备依赖成功改造T细胞,使其较不易受到癌细胞免疫逃逸和抑制,从而减少脱靶毒性。因此,CRISPR/Cas9推动了基于免疫检查点的血液系统恶性肿瘤CAR-T 治疗发展。持续的研究和临床试验将进一步推动该领域进步,最终惠及患者并改善结局。
Hematologic malignancies, which arise from dysregulation of hematopoiesis, are a group of cancers originating in cells with diminished capacity to differentiate into mature progeny and accumulating immature cells in blood-forming tissues such as lymph nodes and bone marrow. Immune- targeted therapies, such as Immune Checkpoint Blockade (ICB), chimeric antigen receptor T (CAR-T) cell therapy, and the Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) system, a precise, popular, and versatile genome engineering tool, has opened new avenues for the treatment of malignancies.
Targeting immune checkpoints has revolutionized FDA approval in cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), PD-1 (programmed death-1), and PDL1. According to the ICB and CAR techniques, the production of efficient CAR-T cells depends on the successful genetic modification of T cells, making them less susceptible to immune escape and suppression by cancer cells, which results in reduced off-target toxicity.
Therefore, CRISPR/Cas9 has revolutionized the immune checkpoint-based approach for CAR-T cell therapy of hematologic malignancy. Continued research and clinical trials will undoubtedly pave the way for further advances in this field, ultimately benefiting patients and improving outcomes.
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