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:Diffuse Large B-Cell Lymphoma (DLBCL): Early Patient Management and Emerging Treatment Options.
Diffuse Large B-Cell Lymphoma (DLBCL): Early Patient Management and Emerging Treatment Options.
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弥漫性大B细胞淋巴瘤(DLBCL)目前可治愈,采用R-CHOP化学免疫治疗的治愈率约为60%–70%。但仍有30%–40%的患者治疗无应答或复发。自2000年引入R-CHOP以来,强化R-CHOP方案、巩固治疗或维持治疗等多种尝试均未能改善患者结局。对淋巴瘤细胞分子生物学和肿瘤微环境认识的加深,为进一步改善DLBCL患者生存带来了希望。新的分子发现推动了针对驱动基因改变的靶向治疗临床试验,旨在改善高危亚组患者的生存,但初步结果尚不一致。不依赖特定淋巴瘤细胞分子改变的治疗策略包括抗体药物偶联物(尤其是维泊妥珠单抗)、具有免疫调节作用的抗体治疗(他法西他单抗、来那度胺)以及T细胞衔接疗法(双特异性抗体、提前应用CAR-T 细胞)。这些方法有望提高治愈率并改变当前治疗模式。
不过,还需改进预后分层和临床试验设计,并调整终点指标,包括应用循环肿瘤DNA(ctDNA)。本文综述DLBCL管理的复杂性。
Diffuse large B-cell lymphoma (DLBCL) represents a curable disease with a 60-70% chance of cure with current R-CHOP chemoimmunotherapy.
However, 30-40% of patients are refractory or relapsing. Many attempts failed to improve the outcome of DLBCL patients, including the intensification of R-CHOP regimen, consolidation, or maintenance therapy since the introduction of R-CHOP in 2000.
Better understanding of both molecular biology of lymphoma cells and the tumor microenvironment raised the hope for future improvement of DLBCL patients' survival. Novel molecular findings have initiated clinical trials exploring targeted therapy based on driver genetic alterations with an intent to improve survival of high-risk subsets of patients.
But the preliminary results remain ambiguous. The approach "agnostic" to specific molecular alterations of lymphoma cell includes antibody-drug conjugates (especially polatuzumab vedotin), immunotherapy comprising different antibodies with immunomodulatory effect (tafasitamab, lenalidomide), and T-cell engaging therapy (bispecific antibodies, early use of CAR T-cell). This approach could increase the cure rates and change the current therapeutic paradigm.
However, better prognostic stratification, smarter designs of clinical trials, modification of endpoints including the use of ctDNA are needed. This review covers the complexity of DLBCL management.
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