肿瘤细胞治疗研究
英文原题:CAR-T Cell Therapy: Engineering Remission in Refractory Myeloma.
CAR-T Cell Therapy: Engineering Remission in Refractory Myeloma.
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嵌合抗原受体(CAR)T 细胞已迅速重塑了复发/难治性多发性骨髓瘤(MM)的治疗格局,从实验性挽救治疗选择进展为一种已证实具有总生存期优势、并可使部分患者获得持久甚至潜在治愈性缓解的疗法。本综述梳理了支持其应用的当前证据、其成功与失败背后的生物学机制、已确立和新兴的毒性反应,以及将在未来数年定义该领域的新型方法。针对 B 细胞成熟抗原(BCMA)的已获批产品即使在经过大量既往治疗的患者中也能诱导快速而深度的缓解,长期随访现在提示,相当一部分患者在不接受维持治疗的情况下,单次输注后可获得长期缓解。
Chimeric antigen receptor (CAR) T cells have rapidly reshaped the treatment of relapsed and refractory multiple myeloma (MM), progressing from an experimental salvage option to a therapy with a demonstrated overall survival advantage and durable, potentially curative remissions in a subset of patients. This review surveys the current evidence supporting their use, the biology underlying their successes and failures, established and emerging toxicities, and novel approaches that will define the field in the coming years.
Approved products directed against B cell maturation antigen (BCMA) induce rapid and deep responses even in heavily pretreated patients, and long-term follow-up now suggests a meaningful fraction of patients achieve prolonged remission after a single infusion without maintenance therapy. These benefits are accompanied by distinctive toxicities that shape the risk-benefit calculus as therapy moves to earlier lines and even to treatment naïve patients.
We discuss the determinants of response and relapse, as well as the mechanisms of antigen-positive and antigen-negative escape that next-generation approaches aim to overcome. These include novel antigen targets, multi-antigen and armored constructs, rapid manufacturing, and in vivo CAR generation, all with the goal of extending durable remissions to every patient.
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