CD22-targeted CAR T cells induce remission in B-ALL that is naive or resistant to CD19-targeted CAR immunotherapy.
CD22-targeted CAR T cells induce remission in B-ALL that is naive or resistant to CD19-targeted CAR immunotherapy.
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CD22靶向的CAR T细胞在B-ALL中诱导对CD19靶向的CAR免疫疗法具有抗性的B-ALL。
DOI：
10.1038/nm.4441
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发表时间：
2018-01
期刊：
影响因子：
82.9
通讯作者：
Mackall CL
中科院分区：
文献类型：
--
作者：
Fry TJ;Shah NN;Orentas RJ;Stetler-Stevenson M;Yuan CM;Ramakrishna S;Wolters P;Martin S;Delbrook C;Yates B;Shalabi H;Fountaine TJ;Shern JF;Majzner RG;Stroncek DF;Sabatino M;Feng Y;Dimitrov DS;Zhang L;Nguyen S;Qin H;Dropulic B;Lee DW;Mackall CL
靶向CD19的嵌合抗原受体（CAR） t细胞介导复发/难治性前b细胞急性淋巴细胞白血病（B-ALL）的有效作用，但抗原丢失是CD19靶向免疫治疗耐药的常见原因。CD22也在大多数B-ALL上表达，通常在CD19丢失后保留。我们报告了一项I期试验的结果，该试验在21名儿童和成人中测试了一种新型CD22-CAR，其中包括17名先前接受过cd19定向免疫治疗的儿童和成人。剂量依赖性抗白血病活性观察到73%（11/15）接受≥1 × 106 CD22-CART细胞/kg治疗的患者完全缓解，包括5/5 CD19dim/阴性B-ALL患者。中位缓解期为6个月。复发与CD22位点密度降低有关，这可能使CD22- cart细胞逃脱了杀伤。这些结果首次确定了CD22-CAR在b细胞前ALL中的临床活性，包括抗cd19免疫治疗的白血病，在b细胞前ALL中显示出与CD19-CART生物活性剂量相当的效力。他们还强调了抗原密度在调节CAR功能中所起的关键作用。（NCI校内研究计划资助）
Chimeric antigen receptor (CAR) T-cells targeting CD19 mediate potent effects in relapsed/refractory pre-B cell acute lymphoblastic leukemia (B-ALL) but antigen loss is a frequent cause of resistance to CD19-targeted immunotherapy. CD22 is also expressed on most B-ALL and usually retained following CD19 loss. We report results from a phase I trial testing a novel CD22-CAR in twenty-one children and adults, including 17 previously treated with CD19-directed immunotherapy. Dose dependent anti-leukemic activity was observed with complete remission in 73% (11/15) of patients receiving ≥ 1 × 106 CD22-CART cells/kg, including 5/5 patients with CD19dim/neg B-ALL. Median remission duration was 6 months. Relapses were associated with diminished CD22 site density that likely permitted escape from killing by CD22-CART cells. These results are the first to eastablish the clinical activity of a CD22-CAR in pre-B cell ALL, including in leukemia resistant to anti-CD19 immunotherapy, demonstrating comparable potency to CD19-CART at biologically active doses in B-ALL. They also highlight the critical role played by antigen density in regulating CAR function. (Funded by NCI Intramural Research Program)
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影响因子：
6.2
作者：
Faderl S;O'Brien S;Pui CH;Stock W;Wetzler M;Hoelzer D;Kantarjian HM
通讯作者：
Kantarjian HM
影响因子：
6.2
作者：
Grant, Barbara W.;Jung, Sin-Ho;Johnson, Jeffrey L.;Kostakoglu, Lale;Hsi, Eric;Byrd, John C.;Jones, Jeffrey;Leonard, John P.;Martin, S. Eric;Cheson, Bruce D.
通讯作者：
Cheson, Bruce D.
影响因子：
16.6
作者：
Jacoby E;Nguyen SM;Fountaine TJ;Welp K;Gryder B;Qin H;Yang Y;Chien CD;Seif AE;Lei H;Song YK;Khan J;Lee DW;Mackall CL;Gardner RA;Jensen MC;Shern JF;Fry TJ
通讯作者：
Fry TJ
影响因子：
82.9
作者：
Long, Adrienne H.;Haso, Waleed M.;Shern, Jack F.;Wanhainen, Kelsey M.;Murgai, Meera;Ingaramo, Maria;Smith, Jillian P.;Walker, Alec J.;Kohler, M. Eric;Venkateshwara, Vikas R.;Kaplan, Rosandra N.;Patterson, George H.;Fry, Terry J.;Orentas, Rimas J.;Mackall, Crystal L.
通讯作者：
Mackall, Crystal L.
影响因子：
51.1
作者：
Kantarjian, Hagop;Thomas, Deborah;O'Brien, Susan
通讯作者：
O'Brien, Susan