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:CD19 CAR-T Cell Therapy for Relapsed or Refractory Nodal and Gastrointestinal Follicular Lymphoma: Current Advances and Future Perspectives.
CD19 CAR-T Cell Therapy for Relapsed or Refractory Nodal and Gastrointestinal Follicular Lymphoma: Current Advances and Future Perspectives.
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滤泡性淋巴瘤(FL)是最常见的惰性B细胞淋巴瘤,然而原发性胃肠道FL(GI-FL)仍定义不清,复发/难治性病例的治疗存在争议。本综述旨在批判性评估CD19靶向嵌合抗原受体(CAR)T细胞疗法在结直肠FL和GI-FL中的作用,重点介绍关键临床试验及GI受累的独特生物学考量。
ZUMA-5、ELARA 和 TRANSCEND FL 等关键试验已证明,在复发/难治性 FL 患者中具有较高的总缓解率和完全缓解率,以及持久的无进展生存期。尤其是 liso-cel 已显示出有利的疗效-毒性平衡,包括在转化性疾病或 24 个月内进展(POD24)的患者中。然而,针对 GI-FL 的特定数据仍然稀缺,新出现的证据表明,其微环境、免疫检查点表达和突变谱可能以不同于结内 FL 的方式影响 CAR-T 应答。CD19 CAR-T 疗法代表了复发/难治性 FL 的重大治疗进展,并为晚期或高危 GI-FL 患者带来了希望。尽管如此,GI-FL 的罕见性、专门的临床数据有限,以及治疗相关毒性、成本和可及性等挑战,仍需要进一步开展前瞻性研究。整合基于生物标志物的患者选择和 GI-FL 特异性试验设计,对于优化 CAR-T 疗法在这一独特亚型中的应用将至关重要。
PURPOSE OF REVIEW: Follicular lymphoma (FL) is the most common indolent B-cell lymphoma, yet primary gastrointestinal FL (GI-FL) remains poorly defined, and treatment of relapsed/refractory cases is controversial. This review aims to critically evaluate the role of CD19-directed chimeric antigen receptor (CAR) T-cell therapy in nodal and GI-FL, highlighting key clinical trials and the unique biological considerations of GI involvement.
RECENT FINDINGS: Pivotal trials such as ZUMA-5, ELARA, and TRANSCEND FL have demonstrated high overall and complete response rates with durable progression-free survival in patients with relapsed/refractory FL. Liso-cel in particular has shown a favourable efficacy-toxicity balance, including in patients with transformed disease or progression within 24 months (POD24).
However, data specific to GI-FL are scarce, and emerging evidence suggests that its microenvironment, immune checkpoint expression, and mutational profile may influence CAR-T responses differently from nodal FL. CD19 CAR-T therapy represents a major therapeutic advance for relapsed/refractory FL and holds promise for patients with advanced or high-risk GI-FL.
Nonetheless, the rarity of GI-FL, limited dedicated clinical data, and challenges such as treatment-related toxicities, costs, and accessibility warrant further prospective studies. Integrating biomarker-based patient selection and GI-FL-specific trial designs will be crucial to optimise the application of CAR-T therapy in this distinct subtype.
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