Eshhar Z
Department of Immunology, The Weizmann Institute of Science, Rehovot, Israel.
Handb Exp Pharmacol. 2008(181):329-42. doi: 10.1007/978-3-540-73259-4_14.
"T-bodies" are genetically engineered T cells armed with chimeric receptors whose extracellular recognition unit is comprised of an antibody-derived recognition domain and whose intracellular region is derived from lymphocyte stimulating moiety(ies). The structure of the prototypic chimeric receptor, also known as a chimeric immune receptor, is modular, designed to accomodate various functional domains and thereby to enable choice of specificity and controlled activation of T cells. The preferred antibody-derived recognition unit is a single chain variable fragment (scFv) that combines the specificity and binding residues of both the heavy and light chain variable regions of a monoclonal antibody. The most common lymphocyte activation moieties include a T-cell costimulatory (e.g. CD28) domain in tandem with a T-cell triggering (e.g. CD3zeta) moiety. By arming effector lymphocytes (such as T cells and natural killer cells) with such chimeric receptors, the engineered cell is redirected with a predefined specificity to any desired target antigen, in a non-HLA restricted manner. Chimeric receptor (CR) constructs are introduced ex vivo into T cells from peripheral lymphocytes of a given patient using retroviral vectors. Following infusion of the resulting T-bodies back into the patient, they traffic, reach their target site, and upon interaction with their target cell or tissue, they undergo activation and perform their predefined effector function. Therapeutic targets for the T-body approach include cancer and HIV-infected cells, or autoimmune effector cells. To date, the most investigated area is cancer therapy. Here, the T-bodies are advantageous because their tumor recognition is not HLA-specific and, therefore, the same constructs can be used for a wide spectrum of patients and cancers.
“T 细胞载体”是经过基因工程改造的 T 细胞，配备嵌合受体，其细胞外识别单元由抗体衍生的识别域组成，细胞内区域则来源于淋巴细胞刺激部分。原型嵌合受体，也称为嵌合免疫受体，其结构是模块化的，旨在容纳各种功能域，从而能够选择特异性并控制 T 细胞的激活。优选的抗体衍生识别单元是单链可变片段（scFv），它结合了单克隆抗体重链和轻链可变区的特异性和结合残基。最常见的淋巴细胞激活部分包括与 T 细胞触发部分（如 CD3ζ）串联的 T 细胞共刺激（如 CD28）域。通过用这种嵌合受体武装效应淋巴细胞（如 T 细胞和自然杀伤细胞），工程细胞以预定的特异性被重定向到任何所需的靶抗原，且不受 HLA 限制。使用逆转录病毒载体将嵌合受体（CR）构建体体外导入给定患者外周淋巴细胞的 T 细胞中。将产生的 T 细胞载体回输到患者体内后，它们会迁移到靶位点，与靶细胞或组织相互作用后，它们会被激活并执行预定的效应功能。T 细胞载体方法的治疗靶点包括癌症和 HIV 感染细胞，或自身免疫效应细胞。迄今为止，研究最多的领域是癌症治疗。在这方面，T 细胞载体具有优势，因为它们对肿瘤的识别不具有 HLA 特异性，因此，相同的构建体可用于广泛的患者和癌症类型。
