淋巴細胞瘤逃避CD-19靶向的嵌合抗原受體修飾的T細胞的進化

淋巴細胞瘤逃避CD-19靶向的嵌合抗原受體修飾的T細胞的進化

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.
淋巴細胞瘤逃避CD-19靶向的嵌合抗原受體修飾的T細胞的進化
總結：
一個患有復發(fā)性和難治性慢性淋巴細胞白血病伴隨Richter轉化的病人接受CAR修飾的靶向CD19的T細胞治療，但是之后復發(fā)了與克隆相關的漿母細胞性淋巴瘤。因為對預漿細胞或B淋巴細胞分化zui常規(guī)的標記物的損失（包括CD19），通過與正常細胞相比不同的途徑，增強了這種成熟淋巴細胞瘤逃脫譜系特異性靶向*的能力。分子遺傳評價表明CD-19陰型疾病具有多個獨立的因素，zui終在這個病人身上發(fā)生。隨著時間的推移，當把這些修飾的T細胞施加的選擇性壓力作為一種測試的話，這種生物體對環(huán)境的適應性意味著著潛在的對CAR-T細胞治療的挑戰(zhàn)。
關鍵詞：白血病，慢性淋巴細胞白血病，淋巴瘤，漿母細胞，嵌合抗原受體的T細胞。