不适合移植的大 B 细胞淋巴瘤二线使用 axicabtagene ciloleucel:ALYCANTE 最终分析
Second-line axicabtagene ciloleucel in large B-cell lymphoma ineligible for transplantation: ALYCANTE final analysis.
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:Finding the Sweet Spot for the Treatment of B Cell Malignancies.
Finding the Sweet Spot for the Treatment of B Cell Malignancies.
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细胞聚糖谱具有高度多样性,是通过称为糖基化的过程连接至蛋白质(糖蛋白)和脂质(糖脂)的多种糖基组成。癌细胞通常携带异常糖链,这些糖链有望用于癌症诊断、预后判断及新型治疗策略开发。本综述聚焦恶性B细胞(包括B细胞淋巴瘤和白血病)的差异性糖基化模式。已知的恶性B细胞异常糖链谱包括滤泡性淋巴瘤(FL)B细胞受体(BCR)中获得性高甘露糖型N-聚糖,以及伯基特淋巴瘤(BL)中糖鞘脂Gb3/CD77表达增加。可利用特异性识别这些糖链且本身具有细胞毒性的凝集素,或将凝集素制成药物偶联形式,以此靶向治疗。此外,调节糖链,尤其是唾液酸,还可增强免疫治疗效果。将糖链用于免疫治疗靶向也具有潜力,可应用于相对较新的嵌合抗原受体(CAR)T细胞疗法,该疗法治疗多种B细胞恶性肿瘤已相当有效。因此,恶性B细胞的糖链谱蕴含众多治疗靶向机会。预计进一步深入分析糖链特征将为B细胞恶性肿瘤治疗带来更多可能性。
The glycan profile of cells comprises a high variety of sugar moieties that are attached to proteins (glycoproteins) and lipids (glycolipids) via a process called 'glycosylation'. Cancer cells commonly carry aberrant glycans, which may be of interest for cancer diagnosis, prognosis, as well as the development of novel therapeutic strategies. This review focuses on the differential glycosylation patterns on malignant B cells, including both B cell lymphoma and leukemia.
Well-known aberrant glycan profiles on malignant B cells include acquired high mannose N-glycans in the B cell receptor (BCR) of follicular lymphoma (FL), and increased expression of the glycosphingolipid Gb3/CD77 on Burkitt's lymphoma (BL). These structures can be exploited for therapy by using lectins that specifically recognize these patterns with intrinsic cytotoxic activity or in a drug-conjugate format.
Furthermore, immunotherapy can be improved by modulating glycans, especially sialic acids. Targeting glycans for immunotherapy is also of interest for chimeric antigen receptor (CAR) T cell therapy, a relatively novel therapy that has been quite effective in various B cell malignancies.
Thus, the glycan profile of malignant B cells harbors many opportunities for therapeutic targeting. It is anticipated that further in-depth glycan profiling will open up many more opportunities for the treatment of B cell malignancies.
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