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:Classical Hodgkin Lymphoma Today.
经典霍奇金淋巴瘤是全球范围内最可治愈的肿瘤之一,尤其是在年轻成人中。
经典霍奇金淋巴瘤是全球范围内最可治愈的肿瘤之一,尤其是在年轻成人中。在最大化治疗疗效和最小化急性及长期毒性方面已取得重大进展,包括不孕、心血管并发症和第二原发恶性肿瘤。治疗前预后分层和中期PET反应是个体化治疗策略的基石。循环肿瘤游离DNA是一种用于诊断时霍奇金淋巴瘤基因分型和监测治疗反应的研究性工具。短程联合化疗后序贯受累部位/受累淋巴结放疗仍是早期疾病的金标准,而联合化疗仍是晚期疾病治疗的主要手段,可联合或不联合新型药物,如抗CD30抗体药物偶联物brentuximab-vedotin(BV)或抗PD1检查点抑制剂(CPI)nivolumab和pembrolizumab。在老年患者中,治疗需要谨慎调整以最小化急性毒性,通常减少化疗负荷或纳入新的靶向治疗。尽管化疗敏感复发/难治性cHL患者中挽救化疗后自体干细胞移植(ASCT)巩固仍是标准方法,但当BV和CPI在ASCT前整合入挽救方案或作为移植后维持治疗时,缓解率和缓解持续时间已取得显著改善。这两类药物也被批准作为不适合移植或患有难治/复发疾病患者的单药治疗。新型治疗方法,包括抗CD30 CAR-T细胞以及抗CD30/CD16A双特异性抗体AFM13与预激活的同种异体脐带血来源NK细胞联合使用,正在对已失败于当前获批治疗选择的患者进行研究。
Classical Hodgkin Lymphoma is one of the most curable neoplasms worldwide, particularly among young adults. Significant advances have been made to maximize treatment efficacy and minimize acute and long-term toxicities, including infertility, cardiovascular complications and secondary primary malignancies. Pretreatment prognostic stratification and interim PET response are the cornerstones of personalized treatment strategies. Circulating tumor cell-free DNA represents an investigational tool for genotyping Hodgkin Lymphoma at diagnosis and monitoring treatment response. An abbreviated course of polychemotherapy followed by involved-site/involved nodal radiotherapy continues to be the gold standard in early-stage diseases, while polychemotherapy remains the mainstay for the treatment of advanced-stage disease with or without the incorporation of novel agents, such as the anti-CD30 antibody-drug conjugate brentuximab-vedotin (BV) or the anti-PD1 checkpoint inhibitors (CPI) nivolumab and pembrolizumab. In elderly patients, treatment requires careful adaptation to minimize acute toxicities, often reducing the chemotherapy load or incorporating new targeted therapies. Although consolidation with autologous stem cell transplantation (ASCT) after salvage chemotherapy remains the standard approach in patients with chemosensitive relapsed/refractory cHL, significant improvements in response rate and duration have been achieved when BV and CPI are integrated into salvage regimens prior to ASCT or as post-transplant maintenance. Both classes of drugs are also approved as monotherapy in patients who are transplant-ineligible or have refractory/relapsed disease. Novel therapeutic approaches, including anti-CD30 CAR-T cells and the combination of the anti-CD30/CD16A bispecific antibody AFM13 with preactivated allogeneic cord blood-derived NK cells, are under investigation for patients who have failed the currently approved treatment options.
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