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:Immunotherapy approaches for malignant pleural mesothelioma.
在过去十年中,免疫检查点抑制剂(ICIs)彻底改变了癌症的治疗方式。
在过去十年中,免疫检查点抑制剂(ICIs)彻底改变了癌症治疗。在间皮瘤这种通常由石棉暴露引起、预后极差的罕见癌症中,单药或双药ICIs治疗在一线及复发疾病 setting 中均较既往标准治疗显著改善总生存期。支持ICIs应答的预测性生物学特征仍知之甚少;然而,关于间皮瘤免疫微环境和基因组图谱及其与ICIs应答或获得性耐药相关性的见解正在涌现。多项涉及ICIs与另一种ICI或不同药物联合的合理性联合研究正在进行中,并出现了协同抗肿瘤活性的新证据。非ICI为基础的免疫疗法,如肽基疫苗和靶向间皮素的CAR-T 细胞,已显示出有前景的疗效。此外,树突状细胞疫苗和病毒细胞因子递送等关键试验的结果备受期待。在本综述中,我们全面总结了间皮瘤免疫疗法发展的关键步骤,重点关注已导致随机临床评估的策略以及新出现的应答预测因子。然后,我们预测了正在进行的研究可能带来的未来治疗机会。
Over the past decade, immune-checkpoint inhibitors (ICIs) have revolutionized the treatment of cancer. In mesothelioma, a rare cancer with a dismal prognosis generally caused by exposure to asbestos, treatment with single or dual ICIs results in robust improvements in overall survival over previous standard-of-care therapies, both in the first-line and relapsed disease settings. Predictive biological features that underpin response to ICIs remain poorly understood; however, insights into the immune microenvironment and genomic landscape of mesothelioma as well as into their association with response or acquired resistance to ICIs are emerging. Several studies of rational combinations involving ICIs with either another ICI or a different agent are ongoing, with emerging evidence of synergistic antitumour activity. Non-ICI-based immunotherapies, such as peptide-based vaccines and mesothelin-targeted chimeric antigen receptor T cells, have demonstrated promising efficacy. Moreover, results from pivotal trials of dendritic cell vaccines and viral cytokine delivery, among others, are eagerly awaited. In this Review, we comprehensively summarize the key steps in the development of immunotherapies for mesothelioma, focusing on strategies that have led to randomized clinical evaluation and emerging predictors of response. We then forecast the future treatment opportunities that could arise from ongoing research.
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