决定异体 CAR T 细胞排斥与扩增的细胞和分子机制
Cellular and molecular mechanisms determining allogeneic CAR T cell rejection and expansion.
我们评估了11例接受单一批次cemacabtagene ansegedleucel(cema-cel)治疗的大B细胞淋巴瘤患者,cemacabtagene ansegedleucel是一种异体抗CD19 CAR T产品。
英文原题:Immune checkpoint therapy in pediatric and adolescent lymphomas.
免疫检查点治疗(ICT)旨在释放T淋巴细胞的抗肿瘤活性。
免疫检查点治疗(ICT)旨在释放T淋巴细胞的抗肿瘤活性。细胞毒性T淋巴细胞相关抗原4(CTLA-4)抑制和程序性死亡1(PD-1)抑制是临床癌症治疗中最常用的ICT,它们分别通过阻断抑制信号CTLA-4和程序性死亡配体1(PD-L1)来增强抗肿瘤免疫。在儿童霍奇金淋巴瘤中,ICT在高危和复发疾病中均显示出显著疗效,针对低危疾病疗效的研究正在进行中。儿童成熟B细胞淋巴瘤的PD-L1表达不一,将ICT纳入治疗的经验非常有限。原发性纵隔B细胞淋巴瘤(PMBCL)、间变性大细胞淋巴瘤(ALCL)、侵袭性NK 细胞淋巴瘤(ANKL)以及非特指型外周T细胞淋巴瘤(PTCL, NOS)均一致表达PD-L1,为在这些疾病中使用ICT提供了强有力的生物学依据。在PMBCL中,儿童肿瘤学组(COG)和国家癌症研究所(NCI)国家临床试验网络(NCTN)最近完成了一项随机III期试验,评估nivolumab联合化学免疫治疗用于新诊断PMBCL儿童和成人患者。该试验结果预计于2027年公布。在ALCL和ANKL中,正在进行的临床试验正在评估ICT的疗效。鉴于ICT对儿童霍奇金淋巴瘤的变革性作用,ICT在PD-L1表达增加的多种儿童非霍奇金淋巴瘤亚型中的应用具有重大前景。
Immune checkpoint therapy (ICT) is designed to unleash the anti-tumor activity of Tlymphocytes. Cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) inhibition and programmed death 1 (PD-1) inhibition are the most commonly utilized ICTs in clinical cancer therapy, and they enhance anti-tumor immunity by interrupting the inhibitory signals CTLA-4 and programmed death ligand 1 (PD-L1) respectively. In pediatric Hodgkin lymphoma, ICT has demonstrated remarkable efficacy in both high-risk and relapsed disease, with investigation into the efficacy in low-risk disease ongoing. Pediatric mature B-cell lymphomas have variable expression of PD-L1 with very limited experience incorporating ICT. Primary mediastinal B-cell lymphoma (PMBCL), anaplastic large cell lymphoma (ALCL), aggressive natural killer-cell lymphoma (ANKL), and peripheral T-cell lymphoma, not otherwise specified (PTCL, NOS) all consistently express PD-L1, providing strong biologic rationale for the use of ICT in these diseases. In PMBCL, the Children's Oncology Group (COG) and the National Cancer Institute (NCI) National Clinical Trials Network (NCTN) recently completed a randomized phase III trial of nivolumab in combination with chemo-immunotherapy in children and adults with newly diagnosed PMBCL. Results of this trial are expected in 2027. In ALCL and ANKL, ongoing clinical trials are evaluating the efficacy of ICT. Given the transformational role of ICT for pediatric Hodgkin lymphoma, there is significant promise for the use of ICT in multiple subtypes of pediatric non-Hodgkin lymphoma with increased expression of PD-L1.
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