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.
CAR-T(CAR-T)细胞在血液系统恶性肿瘤中的应用推动了这种免疫治疗形式的显著进展。
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:T-cell acute lymphoblastic leukemia in adults: current treatment approaches and future perspectives.
T-cell acute lymphoblastic leukemia in adults: current treatment approaches and future perspectives.
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有效药物如 venetoclax、bortezomib 和 daratumumab 的可用性可能促成改进的一线治疗方案,这些方案将根据患者的遗传学和药物反应特征进行定制,并且 CAR-T 细胞的相关作用预计将得到发挥,可能超出 R/R 设置。
引言:成人急性淋巴细胞白血病(ALL)的治疗格局因采用反应适应性、借鉴儿童方案的治疗以及 B-ALL 免疫疗法问世而发生显著变化。近年来,对遗传学理解加深、新药结果令人鼓舞,以及单克隆抗体和 CAR-T 细胞显示活性,正为 T-ALL 带来有意义的进展。综述范围:本文讨论成人 T-ALL 当前治疗现状,包括相关化疗骨干方案的依据,并总结具有潜在临床意义的近期生物学进展。
此外,综述新药在复发/难治性(R/R)阶段的研究数据及其向一线治疗推进的情况,并重点关注免疫疗法的新兴作用。专家观点:venetoclax、bortezomib 和 daratumumab 等有效药物有望推动一线方案改善,并根据患者遗传特征和药物应答谱进行个体化设计;预计 CAR-T 也将发挥重要作用,可能扩展至 R/R 阶段以外。中枢神经系统预防以及青年成人和老年患者治疗优化等问题仍需进一步研究,但这些进展最终有望提高疗效、降低毒性并减少异基因造血干细胞移植(allo-HCT)的适用范围。
INTRODUCTION: The therapeutic landscape of acute lymphoblastic leukemia (ALL) in adults has greatly changed thanks to the introduction of response-adapted pediatric-inspired regimens and, in B-ALL, the advent of immunotherapy. More recently, the better understanding of genetics, the encouraging results of new agents and the evidence of activity of monoclonal antibodies and CAR-T cells are opening the road for meaningful advances in T-ALL. AREAS COVERED: We discuss the current therapeutic scenario of T-ALL in adults, including the basis of relevant chemotherapy backbones and a summary of recent biological advances with potential clinical implications.
Besides, we summarize data of new drugs explored in the relapsed/refractory (R/R) setting and how they are moving frontline, including a focus of the emerging role of immunotherapy. EXPERT OPINION: The availability of effective agents like venetoclax, bortezomib and daratumumab may lead to improved frontline regimens, which will be tailored according to patient's genetics and drug response profile, and relevant role of CAR-T cell is foreseen, possibly beyond R/R setting.
While several issues will require further studies, including central nervous system prophylaxis and treatment optimization in young adults and older patients, these advances will ultimately lead to improved efficacy, reduced toxicities and limited indications of allo-HCT.
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