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:CAR T-cells and macrophages in large B-cell lymphoma: impact on toxicity and efficacy.
CAR T-cells and macrophages in large B-cell lymphoma: impact on toxicity and efficacy.
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靶向CD19的嵌合抗原受体(CAR)T细胞疗法是复发/难治性大B细胞淋巴瘤当前的标准治疗,在二线和三线治疗中显示出很高的缓解率。尽管取得这些进展,该治疗策略仍可能引起显著毒性,如细胞因子释放综合征或免疫效应细胞相关神经毒性综合征。虽然这些免疫介导毒性的确切机制尚未明确,近期临床前和临床研究已揭示髓系细胞,尤其是巨噬细胞,在促进治疗疗效和介导毒性方面发挥关键作用。本综述讨论巨噬细胞介导这些效应的现有认识,重点介绍与CAR-T 疗效和副作用相关的巨噬细胞生物学具体机制。这些发现正推动靶向巨噬细胞的新治疗策略,有望在维持CAR-T 疗效的同时减轻毒性。
Chimeric antigen receptor (CAR) T-cell therapy targeting CD19 is the current standard of care for the treatment of relapsed refractory large B cell lymphoma, demonstrating impressive response rates in the second- and third-line setting. Despite these advances, this treatment strategy can result in significant toxicities, such as cytokine release syndrome or immune effector cell associated neurotoxicity syndrome.
While the exact mechanisms of these immune-mediated toxicities are not clearly understood, emerging pre-clinical and clinical studies have revealed the pivotal role of myeloid cells, particularly macrophages, as key contributors to the efficacy of treatments and as crucial mediators of toxicity. In this review, we discuss the current understanding of how macrophages mediate these effects, highlighting specific mechanisms of macrophage biology relevant to CAR T-cell therapy activity and side effects.
These findings are resulting in novel treatment strategies that target macrophages, and able to mitigate toxicity while preserving CAR T-cell therapy efficacy.
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