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淋巴细胞瘤逃避CD-19靶向的嵌合抗原受体修饰的T细胞的进化

更新时间:2016-07-07 点击量:646

淋巴细胞瘤逃避CD-19靶向的嵌合抗原受体修饰的T细胞的进化


Evolution to plasmablastic lymphoma evades CD19-direct ed chimeric antigen receptor T cells
Summary
A patient with relapsed and refractory chronic lymphocytic leukaemia with Richter transformation was treated with chimeric antigen receptor (CAR)-modified T cells targeted for CD19 but later relapsed with a clonally related plasmablastic lymphoma. The loss of most routine markers of pre-plasma cell or B lymphoid differentiation(including CD19) highlights the ability of such mature lymphomas to evade lineage-specific targeted immunotherapy by differentiating along pathways comparable to their normal cellular counterparts. Molecular genetic evaluation demonstrated multiple independent lines of CD19-negative disease that eventually evolved in this single patient. Such plasticity represents potential challenges for antigen- directed CAR-T cell therapy, while serving as a testament to the selective pressure exerted by these engineered T cells over time.
Keywords: leukaemia, chronic lymphocytic leukaemia, plasmablastic, lymphoma,
chimeric antigen receptor T cells.
淋巴细胞瘤逃避CD-19靶向的嵌合抗原受体修饰的T细胞的进化
总结:
一个患有复发性和难治性慢性淋巴细胞白血病伴随Richter转化的病人接受CAR修饰的靶向CD19的T细胞治疗,但是之后复发了与克隆相关的浆母细胞性淋巴瘤。因为对预浆细胞或B淋巴细胞分化zui常规的标记物的损失(包括CD19),通过与正常细胞相比不同的途径,增强了这种成熟淋巴细胞瘤逃脱谱系特异性靶向*的能力。分子遗传评价表明CD-19阴型疾病具有多个独立的因素,zui终在这个病人身上发生。随着时间的推移,当把这些修饰的T细胞施加的选择性压力作为一种测试的话,这种生物体对环境的适应性意味着着潜在的对CAR-T细胞治疗的挑战。
关键词:白血病,慢性淋巴细胞白血病,淋巴瘤,浆母细胞,嵌合抗原受体的T细胞。