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:Advances in Hodgkin Lymphoma Treatment: From Molecular Biology to Clinical Practice.
经典型霍奇金淋巴瘤 (cHL) 是一种高度可治愈的疾病,但约 20% 的患者在标准一线化疗方案后出现进展或复发。
经典霍奇金淋巴瘤(cHL)是一种高度可治愈的疾病,但约 20% 患者在标准一线化疗后出现疾病进展或复发。传统上,这类患者采用挽救治疗方案,随后进行自体干细胞移植。过去十年,随着对 cHL 生物学及肿瘤微环境在疾病进程中作用的认识加深,新型药物进入临床实践,改善了复发/难治性患者的结局。抗 CD30 抗体药物偶联物 brentuximab vedotin 以及 PD-1/PD-L1 检查点抑制剂,现已成为化疗难治患者的治愈性治疗选择;近期随机试验也证实其纳入一线免疫化疗联合方案的疗效。目前正在开发多种可调节患者 T 淋巴细胞和 NK 细胞活性的药物,以及多种抗 CD30 CAR-T 细胞产品。研究人员还在探索多种异常肿瘤表观遗传机制,作为组蛋白去乙酰化酶抑制剂和去甲基化药物等抗肿瘤化合物的靶点。此外,JAK2 抑制联合抗 PD-1 阻断在 cHL 中显示出潜在的互补治疗途径。本综述将总结 cHL 生物学的最新发现、临床可用的新疗法及该领域有前景的未来方向。
Classical Hodgkin Lymphoma (cHL) is a highly curable disease, but around 20% of patients experience progression or relapse after standard frontline chemotherapy regimens. Salvage regimens followed by autologous stem cell transplants represent the historical treatment approach for these cases. In the last decade, with the increasing understanding of cHL biology and tumor microenvironment role in disease course, novel molecules have been introduced in clinical practice, improving outcomes in the relapsed/refractory setting. The anti-CD30 antibody-drug conjugated brentuximab vedotin and PD-1/PD-L1 checkpoint inhibitors represent nowadays curative options for chemorefractory patients, and randomized trials recently demonstrated their efficacy in frontline immune-chemo-combined modalities. Several drugs able to modulate the patients' T-lymphocytes and NK cell activity are under development, as well as many anti-CD30 chimeric antigen receptor T-cell products. Multiple tumor aberrant epigenetic mechanisms are being investigated as targets for antineoplastic compounds such as histone deacetylase inhibitors and hypomethylating agents. Moreover, JAK2 inhibition combined with anti-PD1 blockade revealed a potential complementary therapeutic pathway in cHL. In this review, we will summarize recent findings on cHL biology and novel treatment options clinically available, as well as promising future perspectives in the field.
MEMBER ACCOUNT
登录成功会直接打开下一页。