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:From R-CHOP to revolution: How CAR T-Cells, ADCs, and bispecific antibodies are transforming DLBCL treatment.
From R-CHOP to revolution: How CAR T-Cells, ADCs, and bispecific antibodies are transforming DLBCL treatment.
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新型疗法显著改善了 DLBCL 的结局,但挑战依然存在,包括治疗毒性、可及性以及患者反应的变异性。
弥漫大B细胞淋巴瘤(DLBCL)是最常见且侵袭性最强的非霍奇金淋巴瘤亚型,一线标准治疗为R-CHOP。但许多患者会复发或呈难治性,因此亟需新的治疗方法。近期进展包括嵌合抗原受体(CAR)T细胞疗法、抗体药物偶联物(ADC)、双特异性抗体(bsAb)、免疫调节剂及Exportin-1(XPO-1)抑制剂,已改变治疗策略。
对截至2025年1月PubMed收录文献开展全面综述。系统查阅现有文献后,使用布尔运算符和MeSH术语“Lymphoma”“Large-B-cell”“Diffuse”及DLBCL相关关键词进行检索。
CAR-T 细胞疗法,尤其是阿基仑赛和lisocabtagene maraleucel,显示出更优的无事件生存期和总生存期。polatuzumab vedotin等ADC可改善无进展生存期(PFS),且毒性可管理;glofitamab和epcoritamab等bsAb在复发/难治性DLBCL中显示出较高缓解率。这些新疗法的主要毒性包括细胞因子释放综合征(CRS)和免疫效应细胞相关神经毒性综合征(ICANS)。
新疗法显著改善了DLBCL患者结局,但治疗毒性、可及性和患者应答差异仍是挑战。未来研究应优化联合疗法、寻找可预测治疗应答的生物标志物,并加强毒性管理,以改善患者照护。
Diffuse large B-cell lymphoma (DLBCL) is the most common and aggressive subtype of non-Hodgkin lymphoma, with R-CHOP as the standard first-line treatment. However, many patients experience relapse or refractory disease, prompting the need for new therapeutic approaches. Recent advances, including chimeric antigen receptor (CAR) T-cell therapies, antibody-drug conjugates (ADCs), bispecific antibodies (bsAbs), immunomodulators, and Exportin-1 (XPO-1) inhibitors have transformed treatment strategies.
A comprehensive literature review was conducted using PubMed up to January 2025. Boolean operators and MeSH terms "Lymphoma", "Large-B-cell" and "Diffuse" along with DLBCL-related keywords, were utilized following thorough examination of existing literature.
CAR T-cell therapies, and particularly axicabtagene ciloleucel and lisocabtagene maraleucel, demonstrated superior event-free survival and overall survival. ADCs, such as polatuzumab vedotin, improved PFS with a manageable toxicity profile, while bsAbs like glofitamab and epcoritamab showed high response rates in relapsed or refractory DLBCL. Major toxicities from these new treatments include cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS).
Novel therapies have significantly improved DLBCL outcomes, however challenges remain, including treatment toxicity, accessibility, and variability in patients' response. Future research should aim to optimize combination therapies, identify biomarkers predictive of response, and enhance toxicity management to improve patient care.
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