淋巴細(xì)胞瘤逃避CD-19靶向的嵌合抗原受體修飾的T細(xì)胞的進(jìn)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(xì)胞瘤逃避CD-19靶向的嵌合抗原受體修飾的T細(xì)胞的進(jìn)化
總結(jié)：
一個(gè)患有復(fù)發(fā)性和難治性慢性淋巴細(xì)胞白血病伴隨Richter轉(zhuǎn)化的病人接受CAR修飾的靶向CD19的T細(xì)胞治療，但是之后復(fù)發(fā)了與克隆相關(guān)的漿母細(xì)胞性淋巴瘤。因?yàn)閷?duì)預(yù)漿細(xì)胞或B淋巴細(xì)胞分化zui常規(guī)的標(biāo)記物的損失（包括CD19），通過(guò)與正常細(xì)胞相比不同的途徑，增強(qiáng)了這種成熟淋巴細(xì)胞瘤逃脫譜系特異性靶向*的能力。分子遺傳評(píng)價(jià)表明CD-19陰型疾病具有多個(gè)獨(dú)立的因素，zui終在這個(gè)病人身上發(fā)生。隨著時(shí)間的推移，當(dāng)把這些修飾的T細(xì)胞施加的選擇性壓力作為一種測(cè)試的話(huà)，這種生物體對(duì)環(huán)境的適應(yīng)性意味著著潛在的對(duì)CAR-T細(xì)胞治療的挑戰(zhàn)。
關(guān)鍵詞：白血病，慢性淋巴細(xì)胞白血病，淋巴瘤，漿母細(xì)胞，嵌合抗原受體的T細(xì)胞。