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:Advancing glioblastoma immunotherapy: Molecular pathways and innovative therapeutic strategies.
胶质母细胞瘤(GBM)是一种侵袭性脑肿瘤,预后差,对传统治疗具有耐药性。
胶质母细胞瘤(GBM)是一种侵袭性脑肿瘤,预后差且对传统治疗具有耐药性。GBM 的特征是异常增殖、高生长以及显著免疫抑制的肿瘤微环境(TME),使免疫治疗成为 GBM 的理想治疗方式。免疫治疗领域的最新进展,如疫苗和 CAR-T 细胞治疗,已在加速抗肿瘤免疫反应和改善生存结局方面显示出显著疗效。靶向 CTLA-4 和 PD-1/PD-L1 的免疫检查点药物已显示出增强 T 细胞活化和浸润的协同效应。DCVax-L 等疫苗以及包括 G47 在内的溶瘤病毒已在临床研究中显示出有希望的结果。CAR-T 细胞治疗已针对 EGFRvIII 和 IL13R 2 等特定抗原,并已显示出相当大的抗肿瘤疗效。尽管如此,仍有若干挑战需要考虑,包括免疫抑制性 TME、血脑屏障(BBB)以及 GBM 的分子异质性。应对这些挑战需要一种多方面的策略,包括开发创新联合药物、用于评估治疗疗效的复杂成像方法,以及发现可预测患者对免疫治疗反应的生物标志物。未来的研究可以侧重于突出免疫系统与 GBM 之间复杂的联系,利用临床前模型和临床研究的视角,制定更有效和个性化的治疗方案。本综述着重于近期研究成果和临床数据,为GBM免疫治疗的前景发展提供见解,并强调采取综合策略以改善患者预后的必要性。
Glioblastoma (GBM) has been an aggressive brain tumor and it demonstrates poor prognosis and resistance to the traditional therapeutics. GBM is characterized by abnormal proliferation, high growth, and a significantly immunosuppressive tumor microenvironment (TME), making immunotherapy as an ideal treatment for GBM. The recent advances in the field of immunotherapy such as vaccines, and CAR-T cell treatments, have demonstrated significant efficacy in accelerating anticancer immune responses and improving survival outcomes. Immune checkpoint drugs targeting CTLA-4 and PD-1/PD-L1 have demonstrated synergistic effects in enhancing T cell activation and infiltration. Vaccines such as DCVax-L and oncolytic viruses including G47 have demonstrated promising outcomes in the clinical studies. CAR-T cell treatments have been directed against particular antigens such as EGFRvIII and IL13R 2 and have demonstrated considerable antitumor efficacy. Nonetheless, there are a number of challenges to be considered including the immunosuppressive TME, the blood-brain barrier (BBB), and the molecular heterogeneity of GBM. Addressing these challenges requires a versatile strategy, encompassing the development of innovative combination drugs, complicated imaging methodologies to evaluate treatment efficacy, and the discovery of biomarkers to predict patient responses to immunotherapy. The future research can focus on highlighting the complicated connections between the immune system and GBM, utilizing perspectives from preclinical models and clinical studies to formulate more effective and customized treatment options. This review emphasizes on the recent research results and clinical data, providing insights into prospective developments in GBM immunotherapy and highlighting the necessity of a comprehensive strategy to enhance patient outcomes.
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