The promise and potential pitfalls of chimeric antigen receptors.
The promise and potential pitfalls of chimeric antigen receptors.
复制标题
DOI：
10.1016/j.coi.2009.02.009
复制
发表时间：
2009-04
影响因子：
7
通讯作者：
Rivière I
中科院分区：
文献类型：
--
作者：
Sadelain M;Brentjens R;Rivière I
T细胞工程的一个重要目的是通过抗原特异性受体的遗传转移产生肿瘤靶向T细胞，抗原特异性受体包括生理性mhc限制性T细胞受体（tcr）或非mhc限制性嵌合抗原受体（CARs）。car将抗原特异性和T细胞激活特性结合在一个融合分子中。第一代car包括CD3ζ或Fc受体γ链的胞质区域作为其信号域，有效地重定向T细胞的细胞毒性，但未能使T细胞在重复抗原暴露下增殖和存活。包含CD28和CD3ζ的受体是第二代car的原型，现在正迅速扩展到具有不同功能特性的多种受体。第一代car已在卵巢癌、肾癌、淋巴瘤和神经母细胞瘤患者的I期临床研究中进行了测试，并引起了适度的反应。第二代car正在进入B细胞恶性肿瘤和其他癌症的临床领域，它将为这种方法提供更重要的测试。如果可以避免car的免疫原性，其设计的多功能性和hla独立抗原识别将使car成为T细胞工程开发靶向癌症免疫疗法的首选工具。
One important purpose of T cell engineering is to generate tumor-targeted T cells through the genetic transfer of antigen-specific receptors, which consist of either physiological, MHC-restricted T cell receptors (TCRs) or non MHC-restricted chimeric antigen receptors (CARs). CARs combine antigen-specificity and T cell activating properties in a single fusion molecule. First generation CARs, which included as their signaling domain the cytoplasmic region of the CD3ζ or Fc receptor γ chain, effectively redirected T cell cytotoxicity but failed to enable T cell proliferation and survival upon repeated antigen exposure. Receptors encompassing both CD28 and CD3ζ are the prototypes for second generation CARs, which are now rapidly expanding to a diverse array of receptors with different functional properties. First generation CARs have been tested in phase I clinical studies in patients with ovarian cancer, renal cancer, lymphoma, and neuroblastoma, where they have induced modest responses. Second generation CARs, which are just now entering the clinical arena in the B cell malignancies and other cancers, will provide a more significant test for this approach. If the immunogenicity of CARs can be averted, the versatility of their design and HLA-independent antigen recognition will make CARs tools of choice for T cell engineering for the development of targeted cancer immunotherapies.
登录
查看更多内容
影响因子：
15.9
作者：
Berger, Carolina;Jensen, Michael C.;Riddell, Stanley R.
通讯作者：
Riddell, Stanley R.
影响因子：
3.9
作者：
Beecham, EJ;Ma, QZ;Junghans, RP
通讯作者：
Junghans, RP
影响因子：
4.4
作者：
Barber, Amorette;Zhang, Tong;Sentman, Charles L.
通讯作者：
Sentman, Charles L.
影响因子：
5.1
作者：
Biglari, A;Southgate, TD;Gilham, DE
通讯作者：
Gilham, DE
影响因子：
4.5
作者：
Chang, L.;Chang, W. C.;Jensen, M. C.
通讯作者：
Jensen, M. C.