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:Rethinking Advanced Renal Cell Carcinoma: Integrative Genomics, Immunotherapy, and Molecular-Orthomolecular Strategies.
Rethinking Advanced Renal Cell Carcinoma: Integrative Genomics, Immunotherapy, and Molecular-Orthomolecular Strategies.
肾细胞癌(RCC)被认为是一种异质性恶性肿瘤,其基础是复杂的遗传、代谢和免疫失调。
肾细胞癌(RCC)被认为是一种异质性恶性肿瘤,其基础是复杂的遗传、代谢和免疫失调。特别是,分子研究揭示了独特的致癌机制,这些机制已被利用并作为治疗干预靶点进行研究。这些机制包括缺氧驱动的信号传导、染色体易位以及影响肿瘤进展的基因融合事件。本综述全面概述了这些靶点,并重新思考了RCC的管理。治疗概念包括利用新兴的细胞免疫疗法或靶向分子抑制来靶向基因组融合生物学,并介绍了正分子治疗策略。重点强调了两个临床和病理特征——即易位性RCC中的TFE3融合蛋白以及缺氧诱导因子-2α(HIF-2α)抑制剂在透明细胞RCC中日益重要的作用。我们还介绍了关于新型免疫治疗方法的最新数据,包括基于自体造血干细胞和祖细胞的干扰素-α基因治疗,以及CAR-T 细胞疗法。这些疗法根据其机制原理、转化潜力以及因不良副作用而存在的临床挑战进行了讨论。最后,综述了正分子和天然产物为基础的治疗方法,探讨其作为辅助治疗的潜力,可能用于氧化应激管理、靶向肿瘤代谢和免疫效应,以及提高标准治疗的耐受性。本综述指向一个多维框架,可能支持精准引导RCC管理的进一步研究,因为整合方法可能提高治疗疗效、降低毒性,并支持针对晚期或治疗耐药RCC的个性化干预措施的开发。
Renal cell carcinoma (RCC) is acknowledged as a heterogeneous malignancy underlined by complex genetic, metabolic, and immune dysregulation. In particular, molecular studies have revealed distinct oncogenic mechanisms that have been exploited and studied as therapeutic intervention targets. These include hypoxia-driven signaling, chromosomal translocations, and gene fusion events that affect tumor progression. This review provides a comprehensive overview of these targets and rethinks RCC management. Therapeutic concepts include the targeting of genomic fusion biology with emerging cell-based immunotherapies or targeted molecular inhibition, and orthomolecular therapeutic strategies are presented. Two clinical and pathological features are highlighted-namely, the TFE3 fusion proteins in translocation RCC and the growing role of hypoxia-inducible factor-2α (HIF-2α) inhibitors in clear-cell RCC. We also present recent data on novel immunotherapeutic approaches, including autologous hematopoietic stem and progenitor cell-based interferon-α gene therapy, as well as chimeric antigen receptor T-cell therapy. These therapies are discussed in light of their mechanistic rationale, translational potential, and existing clinical challenges due to unwanted side effects. At last, orthomolecular and natural product-based therapies are reviewed for their potential as adjunctive therapies that might be used for oxidative stress management, the targeting of tumor metabolism and immune effects, and to increase standard treatment tolerance. This review points to a multidimensional framework that might support further research and studies in precision-guided RCC management, as integrative approaches may enhance therapeutic efficacy, reduce toxicity, and support the development of personalized interventions for advanced or treatment-resistant RCC.
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