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:Important Considerations in the Diagnosis and Management of Post-transplant Lymphoproliferative Disorder.
Important Considerations in the Diagnosis and Management of Post-transplant Lymphoproliferative Disorder.
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综述目的:与其他淋巴系统恶性肿瘤相比,移植后淋巴增殖性疾病(PTLD)的分子和临床研究相对不足,长期以来难以确定最佳管理策略。本文通过考察近期风险评估、基因组分析和PTLD靶向治疗试验进展,梳理该领域的最新科学认识。近期发现:多项重要临床试验显示,对于单纯降低免疫抑制无应答的CD20阳性PTLD患者,依据风险分层序贯使用利妥昔单抗(可联合或不联合化疗)是一种合理治疗策略。对复发/难治性EB病毒(EBV)阳性PTLD患者,靶向EBV的细胞毒性淋巴细胞疗法前景良好;但仍需专门临床试验确定如何安全地为PTLD患者实施自体CAR-T 细胞疗法。测序研究强调EBV感染对PTLD发病机制的重要影响,但仍需开展全面的基因组和肿瘤微环境分析,以鉴定能够预测这一临床异质性疾病治疗应答的生物标志物。
PURPOSE OF REVIEW: A relative lack of molecular and clinical studies compared to other lymphoid cancers has historically made it difficult to determine optimal management approaches in post-transplant lymphoproliferative disorder (PTLD).
We sought to better define the "state of the science" in PTLD by examining recent advances in risk assessment, genomic profiling, and trials of PTLD-directed therapy. RECENT FINDINGS: Several major clinical trials highlight risk-stratified sequential therapy incorporating rituximab with or without chemotherapy as a rational treatment strategy in patients with CD20+ PTLD who do not respond to reduction of immunosuppression alone.
Epstein Barr virus (EBV)-targeted cytotoxic lymphocytes are a promising approach in patients with relapsed/refractory EBV+ PTLD, but dedicated clinical trials should determine how autologous chimeric antigen receptor T cell therapy (CAR-T) may be safely administered to PTLD patients. Sequencing studies underscore the important effect of EBV infection on PTLD pathogenesis, but comprehensive genomic and tumor microenvironment profiling are needed to identify biomarkers that predict response to treatment in this clinically heterogeneous disease.
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