Expanded NK cells used for adoptive cell therapy maintain diverse clonality and contain long-lived memory-like NK cell populations.
Expanded NK cells used for adoptive cell therapy maintain diverse clonality and contain long-lived memory-like NK cell populations.
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DOI：
10.1016/j.omto.2022.12.006
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发表时间：
2023-03-16
期刊：
影响因子：
--
通讯作者：
Childs, Richard W.
中科院分区：
文献类型：
--
作者：
Allan, David S. J.;Wu, Chuanfeng;Mortlock, Ryland D.;Chakraborty, Mala;Rezvani, Katayoun;Davidson-Moncada, Jan K.;Dunbar, Cynthia E.;Childs, Richard W.
探索过继性自然杀伤（NK）细胞疗法用于癌症的潜力的多个临床试验已经采用使用饲养细胞的离体扩增来获得大量NK细胞。我们先前已经利用恒河猴模型来克隆追踪移植后条形码转导的CD 34+干细胞和祖细胞的NK细胞后代。在本研究中，使用来自条形码化恒河猴的NK细胞研究在离体扩增期间发生的NK细胞克隆模式的变化，所述离体扩增使用的培养方案类似于在临床制备人NK细胞（包括经辐照的淋巴母细胞系（LCL）饲养细胞或表达4-1BBL和膜结合白细胞介素-21（IL-21）的K562细胞）中使用的培养方案。NK扩增培养物导致克隆多样性NK细胞的增殖，其在第14天收获时含有大于50%的起始条形码库。通过Shannon指数测量的多样性在培养后得以维持。使用LCL和K562饲养细胞，观察到长寿命的推定记忆样NK细胞克隆的增殖，这些克隆继续构成扩增细胞总库的平均31%。这些实验提供了对扩增的NK细胞临床产品的克隆组成的深入了解。Allan及其同事使用移植有条形码转导的造血干细胞和祖细胞的恒河猴来研究在饲养细胞和IL-2存在下通过临床相关的离体培养物扩增的NK细胞的克隆性。扩增的NK细胞保留了克隆多样性和来自长寿命的推定记忆样NK细胞的贡献。
Multiple clinical trials exploring the potential of adoptive natural killer (NK) cell therapy for cancer have employed ex vivo expansion using feeder cells to obtain large numbers of NK cells. We have previously utilized the rhesus macaque model to clonally track the NK cell progeny of barcode-transduced CD34+ stem and progenitor cells after transplant. In this study, NK cells from barcoded rhesus macaques were used to study the changes in NK cell clonal patterns that occurred during ex vivo expansion using culture protocols similar to those employed in clinical preparation of human NK cells including irradiated lymphoblastoid cell line (LCL) feeder cells or K562 cells expressing 4-1BBL and membrane-bound interleukin-21 (IL-21). NK expansion cultures resulted in the proliferation of clonally diverse NK cells, which, at day 14 harvest, contained greater than 50% of the starting barcode repertoire. Diversity as measured by Shannon index was maintained after culture. With both LCL and K562 feeders, proliferation of long-lived putative memory-like NK cell clones was observed, with these clones continuing to constitute a mean of 31% of the total repertoire of expanded cells. These experiments provide insight into the clonal makeup of expanded NK cell clinical products. Allan and colleagues used rhesus macaques transplanted with barcode-transduced hematopoietic stem and progenitor cells to study the clonality of NK cells expanded via clinically relevant ex vivo cultures in the presence of feeder cells and IL-2. Expanded NK cells retained clonal diversity and contributions from long-lived putative memory-like NK cells.
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影响因子：
17.1
作者：
Horowitz A;Strauss-Albee DM;Leipold M;Kubo J;Nemat-Gorgani N;Dogan OC;Dekker CL;Mackey S;Maecker H;Swan GE;Davis MM;Norman PJ;Guethlein LA;Desai M;Parham P;Blish CA
通讯作者：
Blish CA
影响因子：
2.3
作者：
Fagerland, Morten W.;Lydersen, Stian;Laake, Petter
通讯作者：
Laake, Petter
影响因子：
2.7
作者：
Gomez Garcia, Lara Maria;Escudero, Adela;Perez-Martinez, Antonio
通讯作者：
Perez-Martinez, Antonio
影响因子：
15.9
作者：
Khatua, Soumen;Cooper, Laurence J. N.;Gopalakrishnan, Vidya
通讯作者：
Gopalakrishnan, Vidya
影响因子：
11.2
作者：
Fujisaki H;Kakuda H;Shimasaki N;Imai C;Ma J;Lockey T;Eldridge P;Leung WH;Campana D
通讯作者：
Campana D