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:Liver transplantation for hepatocellular carcinoma following immunotherapy.
Liver transplantation for hepatocellular carcinoma following immunotherapy.
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综述目的:探讨免疫检查点抑制剂(ICI)在适合接受肝移植(LT)的肝细胞癌(HCC)患者中的新兴应用,特别是作为移植桥接和降期治疗,并讨论将ICI整合至移植方案面临的临床挑战,包括移植物排斥、免疫相关毒性和证据缺口。最新发现:ICI作为LT前的桥接和降期治疗显示出潜力;多中心研究报告降期成功率为75.6%、LT术后3年生存率为85%、排斥相关死亡率为7.2%。停药间隔超过94天和年龄较大被认为是降低同种异体移植物排斥风险的保护因素。EMERALD-1和LEAP-012试验证明,局部区域治疗联合ICI有效;ICI联合经动脉化疗栓塞(TACE)后,无进展生存期分别改善至15.0个月和14.6个月。同样,结合TACE、立体定向体部放疗(SBRT)和阿维鲁单抗的STAR-FIT II期试验显示完全缓解率为42%,有12%的患者转为接受根治性治疗。毒性和排斥风险仍是主要挑战。总结:ICI是扩大HCC患者移植资格的一种有前景的手段,但将其纳入LT治疗路径仍较复杂。特别是治疗时机和免疫调节相关的安全性问题需要谨慎评估。需开展前瞻性研究并开发生物标志物以指导临床决策。CAR-T 细胞等新型疗法未来可能提供更具靶向性的治疗方法。
PURPOSE OF REVIEW: To explore the emerging use of immune checkpoint inhibitors (ICIs) in hepatocellular carcinoma (HCC) patients eligible for liver transplantation (LT), particularly as bridging and downstaging therapies. This review also addresses the clinical challenges of integrating ICIs into transplant protocols, including graft rejection, immune-related toxicities, and gaps in evidence. RECENT FINDINGS: ICIs have shown potential as bridging and downstaging therapies before LT, with multicentric studies reporting 75. 6% successful downstaging, 85% 3-year post-LT survival, and 7. 2% rejection-related mortality. A washout interval >94 days and older age have been identified as protective factors against allograft rejection.
Combining locoregional therapies with ICIs has proven effective in the EMERALD-1 and LEAP-012 trials, which demonstrated improved progression-free survival (15. 0 and 14. 6 months, respectively) with ICI-TACE combinations. Similarly, the STAR-FIT phase II trial, combining TACE, SBRT, and avelumab, showed a 42% complete response rate and 12% conversion to curative therapy. Toxicity and rejection risk remain major challenges.
SUMMARY: ICIs represent a promising tool for expanding transplant eligibility in HCC, but their integration into LT pathways remains complex. Safety concerns, particularly regarding timing and immune modulation, require careful evaluation. Prospective studies and biomarker development are needed to guide clinical decision-making. Novel therapies such as CAR-T cells may offer more targeted approaches in the future.
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