Decade-long leukaemia remissions with persistence of CD4(+) CAR T cells.
Decade-long leukaemia remissions with persistence of CD4(+) CAR T cells.
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DOI：
10.1038/s41586-021-04390-6
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发表时间：
2022-03
期刊：
影响因子：
64.8
通讯作者：
中科院分区：
文献类型：
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作者：
针对肿瘤细胞重新编程的T淋巴细胞过继转移已显示出治疗各种癌症的潜力。然而，对输注细胞的长期潜力和克隆稳定性知之甚少。在这里，我们研究了两名慢性淋巴细胞白血病患者的长效CD19重定向嵌合抗原受体(CAR)T细胞，他们在2010年实现了完全缓解。CAR T细胞在输注后十多年仍可检测到，两名患者的病情持续缓解。值得注意的是，在两名患者中都出现了高度激活的CD4+细胞群，在后来的时间点上主导了CAR T细胞群。这一转变反映在CAR T细胞克隆构成的稳定，其克隆谱系由少数克隆主导。单细胞图谱显示，这些长期存在的CD4+CAR T细胞在持续功能激活和增殖的同时表现出细胞毒性特征。此外，纵向分析显示，在最初的应答阶段，一名患者体内有一群伽马增量CAR T细胞显著扩张，并伴有CD8+CAR T细胞。我们对这些意想不到的CAR T细胞群的鉴定和表征为研究CAR T细胞特征提供了新的见解，这些特征与白血病的抗癌反应和长期缓解有关。
The adoptive transfer of T lymphocytes reprogrammed to target tumour cells has demonstrated potential for treatment of various cancers. However, little is known about the long-term potential and clonal stability of the infused cells. Here we studied long-lasting CD19-redirected chimeric antigen receptor (CAR) T cells in two patients with chronic lymphocytic leukaemia who achieved a complete remission in 2010. CAR T cells remained detectable more than ten years after infusion, with sustained remission in both patients. Notably, a highly activated CD4+ population emerged in both patients, dominating the CAR T cell population at the later time points. This transition was reflected in the stabilization of the clonal make-up of CAR T cells with a repertoire dominated by a small number of clones. Single-cell profiling demonstrated that these long-persisting CD4+ CAR T cells exhibited cytotoxic characteristics along with ongoing functional activation and proliferation. In addition, longitudinal profiling revealed a population of gamma delta CAR T cells that prominently expanded in one patient concomitant with CD8+ CAR T cells during the initial response phase. Our identification and characterization of these unexpected CAR T cell populations provide novel insight into the CAR T cell characteristics associated with anti-cancer response and long-term remission in leukaemia.
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DOI：
10.1126/science.aad0501
发表时间：
2016-04-08
期刊：
Science (New York, N.Y.)
影响因子：
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作者：
Tirosh I;Izar B;Prakadan SM;Wadsworth MH 2nd;Treacy D;Trombetta JJ;Rotem A;Rodman C;Lian C;Murphy G;Fallahi-Sichani M;Dutton-Regester K;Lin JR;Cohen O;Shah P;Lu D;Genshaft AS;Hughes TK;Ziegler CG;Kazer SW;Gaillard A;Kolb KE;Villani AC;Johannessen CM;Andreev AY;Van Allen EM;Bertagnolli M;Sorger PK;Sullivan RJ;Flaherty KT;Frederick DT;Jané-Valbuena J;Yoon CH;Rozenblatt-Rosen O;Shalek AK;Regev A;Garraway LA
通讯作者：
Garraway LA
影响因子：
15.9
作者：
Nobles, Christopher L.;Sherrill-Mix, Scott;Bushman, Frederic D.
通讯作者：
Bushman, Frederic D.
影响因子：
45.3
作者：
Frey, Noelle, V;Gill, Saar;Porter, David L.
通讯作者：
Porter, David L.
DOI：
10.1056/nejmoa1407222
发表时间：
2014-10-16
期刊：
The New England journal of medicine
影响因子：
--
作者：
Maude SL;Frey N;Shaw PA;Aplenc R;Barrett DM;Bunin NJ;Chew A;Gonzalez VE;Zheng Z;Lacey SF;Mahnke YD;Melenhorst JJ;Rheingold SR;Shen A;Teachey DT;Levine BL;June CH;Porter DL;Grupp SA
通讯作者：
Grupp SA
带有嵌合抗原受体的T细胞具有有效的抗肿瘤作用，可以在晚期白血病患者中建立记忆。
影响因子：
17.1
作者：
Kalos M;Levine BL;Porter DL;Katz S;Grupp SA;Bagg A;June CH
通讯作者：
June CH