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:Post-Transplant Lymphoproliferative Disease (PTLD) after Allogeneic Hematopoietic Stem Cell Transplantation: Biology and Treatment Options.
Post-Transplant Lymphoproliferative Disease (PTLD) after Allogeneic Hematopoietic Stem Cell Transplantation: Biology and Treatment Options.
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移植后淋巴增殖性疾病(PTLD)是异基因造血干细胞移植(alloHSCT)或实体器官移植(SOT)背景下因免疫抑制而发生的严重并发症。大多数PTLD起源于B细胞,60-80%的病例存在EB病毒(EBV)感染,揭示了潜伏感染在该病发病机制中发挥的核心作用。因此,EBV血清学状态被认为是与PTLD相关的最重要危险因素,同时还包括移植前和移植后T细胞免疫抑制的深度。然而,尽管在发病机制理解方面取得了进展并引入了新的治疗选择,alloHSCT后发生的PTLD仍然是一种特别具有挑战性的疾病,并且对于如何治疗利妥昔单抗难治性病例尚需达成共识。本综述旨在探讨alloHSCT背景下PTLD的发病机制、危险因素和治疗选择,最后聚焦于过继性免疫治疗选择,即EBV特异性细胞毒性T淋巴细胞(EBV-CTL)和CAR-T 细胞。
Post-transplant lymphoproliferative disease (PTLD) is a serious complication occurring as a consequence of immunosuppression in the setting of allogeneic hematopoietic stem cell transplantation (alloHSCT) or solid organ transplantation (SOT). The majority of PTLD arises from B-cells, and Epstein-Barr virus (EBV) infection is present in 60-80% of the cases, revealing the central role played by the latent infection in the pathogenesis of the disease.
Therefore, EBV serological status is considered the most important risk factor associated with PTLDs, together with the depth of T-cell immunosuppression pre- and post-transplant.
However, despite the advances in pathogenesis understanding and the introduction of novel treatment options, PTLD arising after alloHSCT remains a particularly challenging disease, and there is a need for consensus on how to treat rituximab-refractory cases. This review aims to explore the pathogenesis, risk factors, and treatment options of PTLD in the alloHSCT setting, finally focusing on adoptive immunotherapy options, namely EBV-specific cytotoxic T-lymphocytes (EBV-CTL) and chimeric antigen receptor T-cells (CAR T).
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