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:Where do immunotherapies stand in management of acute leukemia in adults?
免疫疗法显著改变了成人急性白血病的治疗格局,尤其是在B细胞急性淋巴细胞白血病(B-ALL)中。
免疫疗法显著改变了成人急性白血病的治疗格局,尤其是在B细胞急性淋巴细胞白血病(B-ALL)中。Blinatumomab和inotuzumab ozogamicin已成为确立的治疗方案,在复发/难治性疾病中提高了缓解率、可测量残留病灶清除率和总生存期,且这些药物正日益被纳入一线治疗。此外,自体CD19嵌合抗原受体(CAR)T细胞疗法显著改善了挽救治疗结局,即使在经过大量预处理的患者中也展现出卓越的缓解率和持久应答。对疾病耐药和复发机制的深入理解正在指导优化联合及序贯治疗方案的开发。在急性髓系白血病(AML)中,gemtuzumab ozogamicin已显示出显著的临床获益,尤其是在分子学定义的亚组中。正在进行的研究聚焦于新型抗体-药物偶联物、免疫细胞衔接器和先进细胞疗法,面临的挑战主要在于选择合适的靶点以及克服免疫抑制性肿瘤微环境。对于T细胞急性淋巴细胞白血病(T-ALL),由于恶性细胞、正常细胞和CAR T细胞之间抗原表达重叠,治疗创新面临独特挑战。目前有前景的早期临床和临床前研究正在评估抗CD38抗体以及主要靶向CD5和CD7的CAR T细胞。本综述强调了免疫疗法如何重塑了各类急性白血病的治疗范式,并着重介绍了B-ALL中的成功经验。这些见解强调了持续创新的必要性,以克服AML和T-ALL中现有的障碍,最终旨在提高患者的预后和生活质量。
Immunotherapies have significantly transformed the treatment landscape of acute leukemia in adults, most notably in B-cell acute lymphoblastic leukemia (B-ALL). Blinatumomab and inotuzumab ozogamicin have become established treatments, enhancing remission rates, measurable residual disease clearance, and overall survival in relapsed/refractory disease, and these agents, are now increasingly incorporated into frontline therapy. Additionally, autologous CD19 chimeric antigen receptor (CAR) T-cell therapy has dramatically improved salvage treatment outcomes, demonstrating exceptional remission rates and durable responses even in heavily pretreated patients. Enhanced understanding of mechanisms underlying disease resistance and relapse is guiding the development of optimized combination and sequential therapeutic approaches. In acute myeloid leukemia (AML), gemtuzumab ozogamicin has shown significant clinical benefits, particularly in molecularly defined subsets. Ongoing research focuses on novel antibody-drug conjugates, immune cell engagers, and advanced cellular therapies, facing challenges primarily in selecting appropriate targets and overcoming the immunosuppressive tumor microenvironment. For T-cell acute lymphoblastic leukemia (T-ALL), therapeutic innovation is confronted with unique challenges due to overlapping antigen expression between malignant, normal, and CAR T-cells. Promising early clinical and preclinical studies are currently evaluating anti-CD38 antibodies and CAR T-cells mostly directed against CD5 and CD7. This review highlights how immunotherapy has reshaped treatment paradigms across acute leukemias, underscoring successful experiences in B-ALL. These insights emphasize the need for continued innovation to overcome existing hurdles in AML and T-ALL, ultimately aiming to enhance patient outcomes and quality of life.
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