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:CRISPR-Edited Cell Lines: A New Era in Functional Oncology Research.
使用 CRISPR-Cas9 对癌细胞系进行基因工程改造,使得精确研究癌细胞对不同药物和治疗的反应成为可能。
利用 CRISPR-Cas9 工程化改造癌细胞系,使研究者能够精确考察癌细胞对不同药物和疗法的反应。重要进展包括:使用 MED12 敲除细胞研究细胞对 BRAF 抑制剂的耐药;构建乳腺癌上皮-间质转化 CRISPR 模型;以及在多种癌细胞系中开展药物基因组学分析。CRISPR 也用于改进免疫治疗,例如破坏 PD-1 和 CTLA-4 等免疫检查点以增强 CAR-T 功能,并调整 T 细胞以识别不同抗原。得益于这些创新,目前可以追踪 NSCLC 和卵巢癌等癌症的演变和表观遗传特征变化,并寻找逆转耐药的策略。未来,整合 AI 分析、单细胞多组学、患者来源类器官和 CRISPR 技术机制,将有助于推动精准肿瘤学并加快制定有效治疗方案。
The use of CRISPR-Cas9 to engineer cancer cell lines has made it possible to precisely examine how cancer cells react to different drugs and therapies. Some of the key improvements are in the use of Mediator Complex Subunit 12 (MED12)-knockout cells to study cell resistance to BRAF inhibitors, CRISPR models of epithelial-mesenchymal transition for breast cancer, and pharmacogenomic analysis in various cancer cell lines. CRISPR is used in immunotherapy to help Chimeric Antigen Receptor T (CAR-T) cells function better by disrupting the immune checkpoints like Programmed Cell Death Protein 1 (PD-1) and Cytotoxic T-lymphocyte- associated protein 4 (CTLA-4) and to adapt T cells to react with various antigens. As a result of these innovations, it is now possible to track how cancers like non-small cell lung cancer (NSCLC) and ovarian cancer evolve, change their epigenetic features, and find strategies to reverse their resistance. Moving forward, integrating AI analytics, single-cell multi-omics, patient-derived organoids, and CRISPR mechanisms will help improve precision oncology and speed up effective treatment planning.
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