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:Novel immunotargets in multiple myeloma: biological relevance and therapeutic potential.
多发性骨髓瘤是一种血液系统恶性肿瘤,其特征是复杂的遗传和微环境因素驱动疾病进展和治疗耐药。
多发性骨髓瘤是一种血液系统恶性肿瘤,其特征是复杂的遗传和微环境因素驱动疾病进展和治疗耐药。尽管针对已确立抗原(如 BCMA、CD38、SLAMF7 和 GPRC5D)的疗法取得了进展,但特定挑战仍然存在,包括抗原逃逸、治疗耐药和脱靶毒性,凸显了对新型治疗方式的迫切需求。表面蛋白质组学和整合组学技术的最新进展使得发现能够应对这些挑战的新表面抗原成为可能。通过靶向具有更高肿瘤特异性和健康组织中更低表达的抗原,新兴免疫靶点提供了新的途径,以最大限度地减少脱靶毒性并降低因抗原丢失或免疫逃逸导致的复发风险。本综述概述了新兴免疫靶点,总结了其生物学功能、在疾病发病机制和免疫逃逸中的作用,以及治疗干预的潜力。我们聚焦于目前处于早期临床开发或临床前阶段的十五个新兴靶点,重点强调 LILRB4、SEMA4A、ITGB7、CCR1 和 CD70 作为最有前景的靶点。这些免疫靶点展现出用于下一代免疫疗法的显著潜力,包括抗体-药物偶联物、双特异性抗体和嵌合抗原受体(CAR)T 细胞疗法。临床前或早期临床研究显示出良好的安全性特征、高肿瘤特异性以及克服免疫耐药的机制,共同表明其具有改善患者预后和减少不良反应的潜力。通过全面总结这些进展,本综述强调了新兴免疫靶点的转化潜力,并为指导创新治疗方法的开发提供了见解,以改善多发性骨髓瘤患者的预后。
Multiple myeloma is a hematologic malignancy characterized by complex genetic and microenvironmental factors that drive disease progression and resistance to treatment. Despite advancements in therapies targeting established antigens, such as BCMA, CD38, SLAMF7, and GPRC5D, specific challenges persist, including antigen escape, treatment resistance, and off-tumor toxicity, highlighting the urgent need for novel therapeutic modalities. Recent advances in surface proteomics and integrative omics technologies have enabled the discovery of new surface antigens with the potential to address the challenges. By targeting antigens with higher tumor specificity and lower expression in healthy tissues, emerging immunotargets offer new avenues to minimize off-tumor toxicity and reduce the risk of relapse due to antigen loss or immune evasion. This review provides an overview of emerging immunotargets, summarizing their biological functions, roles in disease pathogenesis and immune evasion, and potential for therapeutic interventions. We focused on fifteen emerging targets currently in early clinical development or the preclinical phase, highlighting LILRB4, SEMA4A, ITGB7, CCR1, and CD70 as the most promising. These immunotargets demonstrate significant potential for next-generation immunotherapies, including antibody-drug conjugates, bispecific antibodies, and chimeric antigen receptor (CAR) T-cell therapies. Preclinical or early clinical studies show favorable safety profiles, high tumor specificity, and mechanisms to overcome immune resistance, collectively suggesting the potential for improved patient outcomes and reduced adverse effects. By presenting a comprehensive summary of these advances, this review underscores the translational potential of emerging immunotargets and provides insights to guide the development of innovative therapeutic approaches to improve outcomes for multiple myeloma patients.
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