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:Current state-of-the-art of immunotherapy in follicular lymphoma.
Current state-of-the-art of immunotherapy in follicular lymphoma.
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CAR-T 提供短疗程治疗,并可能在无进展生存期方面达到平台期。主要缺点包括费用、可及性、需要淋巴细胞清除以及毒性。BSAB 可“即用型”获得,毒性特征相对较低,并且非常适合联合治疗。两种平台都存在显著的感染风险。关于何时对 FL 使用免疫治疗、疾病负担的影响、再治疗的作用以及最佳序贯/联合方案,仍有未解答的问题。展望未来,该领域需要开发新的预后标志物,重新评估治疗适应证,并专注于尽量减少毒性。
免疫疗法的出现迅速改变了滤泡性淋巴瘤(FL)的治疗格局。涵盖领域:自体CD19CAR-T 细胞产品在三线FL中显示出前所未有的疗效,但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)的发生率较高。双特异性抗体(BSAB)在经过重度预处理的FL患者中实现了深度且持久的缓解,且CRS较轻微,神经毒性极小。BSAB在给药途径、治疗持续时间和CRS预防方面存在差异。检查点抑制剂在FL中的缓解率令人失望。来那度胺和tazametostat在FL中单药活性有限,但与其他形式的免疫疗法具有协同作用。
INTRODUCTION: The advent of immunotherapy has rapidly changed the treatment landscape of follicular lymphoma (FL). AREAS COVERED: Autologous CD19 chimeric antigen receptor T - cell (CAR-T) products show unprecedented efficacy in third-line FL but substantial rates of cytokine release syndrome (CRS) and immune effector cell associated neurotoxicity syndrome (ICANS). Bispecific antibodies (BSAB) achieve deep and durable responses in heavily pretreated FL patients with less severe CRS and minimal neurological toxicity. BSAB have differing routes of administration, treatment duration and CRS prophylaxis. Checkpoint inhibitors show disappointing response rates in FL.
Lenalidomide and tazametostat have modest single agent activity in FL, but synergize with other forms of immunotherapy. EXPERT OPINION: CAR-T offers a short duration of therapy with a potential plateau in progression free survival. Major disadvantages include cost, availability, requirement for lymphodepletion and toxicity. BSAB are available 'off the shelf,' have a comparably lower toxicity profile, and are ripe for combination.
With both platforms, there are significant infectious risks. There are unanswered questions regarding when to use immunotherapy for FL, impact of disease burden, role of re-treatment and optimal sequencing/combinations. Moving forward, the field will need to develop new prognostic markers, reassess treatment indications, and focus on minimizing toxicity.
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