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:Folate Receptor Alpha-A Novel Approach to Cancer Therapy.
叶酸受体(FR)早在几十年前就被发现,同时还有靶向细胞内叶酸代谢的药物,如培美曲塞和甲氨蝶呤。
叶酸受体(FR)在几十年前就被发现,同时被发现的还有靶向细胞内叶酸代谢的药物,如培美曲塞和甲氨蝶呤。叶酸通过该受体被细胞摄取,由于癌细胞过表达该受体,许多抗癌药物也靶向该受体。FR是一种膜结合的糖基磷脂酰肌醇(GPI)锚定糖蛋白,由叶酸受体1(FOLR1)基因编码。FR在DNA合成、细胞增殖、DNA修复和细胞内信号传导中发挥重要作用,这些过程对肿瘤发生都至关重要。与正常组织相比,FR在癌细胞中更为普遍,这使其成为肿瘤治疗的理想靶点。FR存在于多种癌症类型中,包括卵巢癌、非小细胞肺癌(NSCLC)和结肠癌。FR广泛用于抗体药物偶联物、小分子药物偶联物和CAR-T 细胞。目前的溶瘤治疗药物包括mirvetuximab soravtansine,正在进行的临床试验正在研究CAR-T 细胞(CAR-T细胞)和疫苗。此外,FR已被用于众多其他应用,包括作为肿瘤类型鉴定的工具,以及作为预后标志物、化疗耐药的替代指标。因此,FR鉴定已成为精准医学的重要组成部分。
Folate receptor (FR) was discovered many decades ago, along with drugs that target intracellular folate metabolism, such as pemetrexed and methotrexate. Folate is taken up by the cell via this receptor, which also targeted by many cancer agents due to the over-expression of the receptor by cancer cells. FR is a membrane-bound glycosyl-phosphatidylinositol (GPI) anchor glycoprotein encoded by the folate receptor 1 (FOLR1) gene. FR plays a significant role in DNA synthesis, cell proliferation, DNA repair, and intracellular signaling, all of which are essential for tumorigenesis. FR is more prevalent in cancer cells compared to normal tissues, which makes it an excellent target for oncologic therapeutics. FR is found in many cancer types, including ovarian cancer, non-small-cell lung cancer (NSCLC), and colon cancer. FR is widely used in antibody drug conjugates, small-molecule-drug conjugates, and chimeric antigen-receptor T cells. Current oncolytic therapeutics include mirvetuximab soravtansine, and ongoing clinical trials are underway to investigate chimeric antigen receptor T cells (CAR-T cells) and vaccines. Additionally, FR has been used in a myriad of other applications, including as a tool in the identification of tumor types, and as a prognostic marker, as a surrogate of chemotherapy resistance. As such, FR identification has become an essential part of precision medicine.
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