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:Management of systemic lupus erythematosus and antiphospholipid syndrome during CAR-T therapy: insights from two clinical cases.
Management of systemic lupus erythematosus and antiphospholipid syndrome during CAR-T therapy: insights from two clinical cases.
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这些病例表明,对于合并自身免疫性疾病的 DLBCL 患者,CAR-T 治疗是可行的且似乎安全,但需要密切监测和多学科管理。这些发现支持进一步开展临床前和临床研究,探索 CAR-T 治疗作为 DLBCL 合并 SLE 和 APS 患者潜在治疗方法的可能性。
系统性红斑狼疮(SLE)和抗磷脂综合征(APS)是以致病性自身抗体存在为特征的自身免疫性疾病,这些抗体主要由B细胞产生。这两种疾病均为慢性、无法治愈,需要终身治疗。CAR-T 细胞疗法已成为难治性血液系统恶性肿瘤的一种有前景的治疗方法,抗CD19 CAR-T 疗法在复发/难治性弥漫性大B细胞淋巴瘤(DLBCL)中显示出高疗效。抗CD19 CAR-T 疗法诱导的B细胞深度耗竭提示,该治疗可能影响伴有SLE或APS的DLBCL患者的临床病程。
我们报告了两例在本机构接受抗CD19 CAR-T 治疗的DLBCL并同时患有SLE和APS的患者临床病例。我们描述了淋巴增殖性疾病的病程以及血清学演变和CAR-T 治疗前后纵向测量的细胞因子谱。
在两种情况下,CAR-T 治疗均使淋巴增殖性疾病获得了完全且持久的代谢缓解。同时,自身抗体滴度趋于稳定,使得免疫调节治疗得以逐步降级。
Systemic lupus erythematosus (SLE) and antiphospholipid syndrome (APS) are autoimmune disorders marked by the presence of pathogenic autoantibodies predominantly produced by B cells. Both conditions are chronic, incurable, and require lifelong treatment. Chimeric antigen receptor T-cell (CAR-T) therapy has emerged as a promising treatment for refractory hematological malignancies, with anti-CD19 CAR-T therapy demonstrating high efficacy in relapsed or refractory diffuse large B-cell lymphoma (DLBCL). The profound depletion of B cells induced by anti-CD19 CAR-T therapy suggests that this treatment may influence the clinical course of patients with DLBCL and concomitant SLE or APS.
We report two clinical cases of patients diagnosed with both DLBCL and concomitant SLE and APS who underwent anti-CD19 CAR-T therapy at our institution. We describe the lymphoproliferative disease course as well as the serological evolution and longitudinal cytokine profiles measured before and after CAR-T therapy.
In both cases, CAR-T therapy resulted in complete and long-lasting metabolic remission of the lymphoproliferative disorder. Concurrently, autoantibody titers stabilized, permitting stepwise de-escalation of the immunomodulatory treatment.
These cases demonstrate that CAR-T therapy for DLBCL is feasible and appears safe in patients with concomitant autoimmune disease but requires close monitoring and interdisciplinary management. These findings support further preclinical and clinical investigation of CAR-T therapy as a potential therapeutic approach in patients with DLBCL and concomitant SLE and APS.
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