决定异体 CAR T 细胞排斥与扩增的细胞和分子机制
Cellular and molecular mechanisms determining allogeneic CAR T cell rejection and expansion.
我们评估了11例接受单一批次cemacabtagene ansegedleucel(cema-cel)治疗的大B细胞淋巴瘤患者,cemacabtagene ansegedleucel是一种异体抗CD19 CAR T产品。
英文原题:Long-term Remission of Severe Psoriasis Following CD19 CAR-T Cell Therapy for Follicular Lymphoma.
银屑病在CD19 CAR-T细胞治疗四周内消退,并且在没有接受任何银屑病针对性治疗的情况下,已保持缓解超过4.5年。
银屑病是一种慢性、免疫介导的炎症性疾病,尽管有高效的生物制剂治疗,但很少能实现持久的、无需治疗的缓解。我们报告一例60岁女性,有49年重度、治疗难治性斑块状银屑病病史,在接受自体CD19靶向嵌合抗原受体(CAR)T细胞治疗滤泡性淋巴瘤后,实现了完全且持续的疾病清除。银屑病在CD19 CAR-T细胞治疗后四周内消退,并已保持缓解超过4.5年,未接受任何针对银屑病的治疗。这一观察结果与新兴报道一起提示,在银屑病中深度清除组织中的B淋巴谱系细胞可能诱导长期的疾病修饰。在机制上,CD19 CAR-T治疗比抗CD20方法靶向更广泛的B细胞群体,可能破坏致病性B-T细胞相互作用和自身反应性免疫环路。这些发现挑战了当前以T细胞为中心的银屑病范式,并支持探索以B细胞为靶点的免疫重置策略,作为实现持久缓解或治愈的途径。
Psoriasis is a chronic, immune-mediated inflammatory disease in which durable, treatment-free remission is rarely achieved despite highly effective biologic therapies. We report a 60-year-old woman with a 49-year history of severe, treatment-refractory plaque psoriasis who developed complete and sustained disease clearance following autologous CD19-directed chimeric antigen receptor (CAR) T-cell therapy for follicular lymphoma. Psoriasis resolved within four weeks of CD19 CAR-T-cell therapy and has remained in remission for over 4.5 years without any psoriasis-directed treatment. This observation, together with emerging reports, suggests that deep tissue depletion of B-lymphoid lineage cells in psoriasis may induce long-term disease modification. Mechanistically, CD19 CAR-T therapy targets a broader spectrum of B-cell populations than anti-CD20 approaches, potentially disrupting pathogenic B-T cell interactions and autoreactive immune circuits. These findings challenge the prevailing T cell-centric paradigm of psoriasis and support exploration of B-cell-directed, immune reset strategies as a route towards durable remission or cure.
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