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:The PDPK1-RSK2 axis as a potential convergent therapeutic vulnerability in B-cell lymphomas.
PDPK1/RSK2轴在几乎所有BCL亚型中均被激活,并可能在疾病发生中发挥重要作用。这表明,尽管各亚型在遗传和表型上存在差异,仍有可能开发出跨亚型有效的治疗方法。靶向一个共享的信号通路可能有助于克服传统精准医学中出现的耐药性,并支持针对罕见病亚型的新疗法开发。然而,由于目前研究仍处于临床前阶段,还需开展更多工作。
B 细胞淋巴瘤(BCL)是最常见的血液系统恶性肿瘤,包含多种亚型,每种亚型因起源细胞、遗传学和病因学的不同而具有独特的临床病程。近年来,亚型特异性免疫化疗、靶向治疗和细胞免疫治疗的进展改善了 BCL 的预后;然而,部分病例仍对现有治疗耐药。为应对这些耐药疾病状态,尤其是跨多种亚型的情况,开发新的通用靶向治疗可能具有变革性意义。涵盖领域:本综述首先强调 PDPK1/RSK2 信号轴的独特之处,概述其正常生物学功能,并简要探讨其在实体瘤中的作用。随后将焦点缩小至 BCL,并辅以我们关于通路激活、功能依赖性、预后价值及早期药物开发的研究证据。
INTRODUCTION: B-cell lymphomas (BCLs) are the most prevalent group of hematologic cancers, encompassing various subtypes, each with a distinct clinical course shaped by cell of origin, genetics, and etiology. Recent advances in subtype-specific immunochemotherapy, targeted therapies, and cellular immunotherapy have improved outcomes for BCLs; nonetheless, some cases remain resistant to existing treatments. To address these resistant disease states, especially across multiple subtypes, the development of new universal targeted therapies could be transformative. AREAS COVERED: This review first highlights what distinguishes the PDPK1/RSK2 signaling axis, outlines its normal biological functions, and briefly examines its roles in solid tumors. It then narrows the focus to BCLs, supported by evidence from our research on pathway activation, functional dependence, prognostic value, and early-stage drug development. EXPERT OPINION: The PDPK1/RSK2 axis is activated in nearly all BCL subtypes and likely plays a significant role in disease development. This suggests the potential for treatments that work across subtypes, despite their genetic and phenotypic differences. Targeting a shared signaling pathway might help overcome resistance seen with traditional precision medicine and support the development of new therapies for rare disease subtypes. However, because current research remains preclinical, more work is necessary.
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