Nanobody Based Dual Specific CARs.
Nanobody Based Dual Specific CARs.
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DOI：
10.3390/ijms19020403
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发表时间：
2018-01-30
影响因子：
5.6
通讯作者：
Vandekerckhove B
中科院分区：
文献类型：
--
作者：
De Munter S;Ingels J;Goetgeluk G;Bonte S;Pille M;Weening K;Kerre T;Abken H;Vandekerckhove B
最近的临床试验表明，过继性嵌合抗原受体（CAR） T细胞疗法是治疗B细胞白血病和淋巴瘤的一种非常有效和可能治愈的选择。然而，靶向单一抗原可能是不够的，并且由于抗原阴性白血病细胞的出现可能会发生复发。对抗抗原逃逸变异体生长的潜在策略是通过串联结合多个抗原识别域来扩大CAR的特异性。作为概念的证明，我们在这里描述了一种双特异性CAR，其中单链可变片段（scFv）被两个单抗体结构域或纳米体（nanoCAR）的串联所取代。在逆转录病毒转导的T细胞中观察到高膜纳米car表达水平。CD20和HER2特异性纳米car与同时表达任一抗原或两种抗原的转基因Jurkat细胞孵育后，可诱导T细胞活化、细胞因子产生和肿瘤裂解。纳米体技术的使用允许生产具有双重特异性和预定义亲和力的紧凑型car。
Recent clinical trials have shown that adoptive chimeric antigen receptor (CAR) T cell therapy is a very potent and possibly curative option in the treatment of B cell leukemias and lymphomas. However, targeting a single antigen may not be sufficient, and relapse due to the emergence of antigen negative leukemic cells may occur. A potential strategy to counter the outgrowth of antigen escape variants is to broaden the specificity of the CAR by incorporation of multiple antigen recognition domains in tandem. As a proof of concept, we here describe a bispecific CAR in which the single chain variable fragment (scFv) is replaced by a tandem of two single-antibody domains or nanobodies (nanoCAR). High membrane nanoCAR expression levels are observed in retrovirally transduced T cells. NanoCARs specific for CD20 and HER2 induce T cell activation, cytokine production and tumor lysis upon incubation with transgenic Jurkat cells expressing either antigen or both antigens simultaneously. The use of nanobody technology allows for the production of compact CARs with dual specificity and predefined affinity.
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影响因子：
11.5
作者：
Kershaw, Michael H.;Westwood, Jennifer A.;Hwu, Patrick
通讯作者：
Hwu, Patrick
影响因子：
10.1
作者：
Hudecek M;Sommermeyer D;Kosasih PL;Silva-Benedict A;Liu L;Rader C;Jensen MC;Riddell SR
通讯作者：
Riddell SR
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：
30.5
作者：
Chang VT;Fernandes RA;Ganzinger KA;Lee SF;Siebold C;McColl J;Jönsson P;Palayret M;Harlos K;Coles CH;Jones EY;Lui Y;Huang E;Gilbert RJC;Klenerman D;Aricescu AR;Davis SJ
通讯作者：
Davis SJ
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.