Monoclonal TCR-redirected tumor cell killing
Monoclonal TCR-redirected tumor cell killing
复制标题
DOI：
10.1038/nm.2764
复制
发表时间：
2012-06-01
期刊：
影响因子：
82.9
通讯作者：
Jakobsen, Bent K.
中科院分区：
文献类型：
--
作者：
Liddy, Nathaniel;Bossi, Giovanna;Jakobsen, Bent K.
T细胞免疫可以潜在地根除恶性细胞，并导致少数癌症患者的临床缓解。然而，在大多数这些个体中，特异性T细胞受体（TCR）介导的免疫识别和激活过程失败。在这里，我们描述的工程和表征的新试剂称为免疫动员单克隆TCRs抗癌（ImmTACs）。四个这样的immtac，每一个都包含一个独特的肿瘤相关表位特异性单克隆TCR，具有皮摩尔亲和力，与人源化CD3特异性单链抗体片段（scFv）融合，有效地重定向T细胞杀死表达极低表面表位密度的癌细胞。此外，这些试剂在体内有效地抑制肿瘤生长。因此，immtac克服了对癌症的免疫耐受，代表了肿瘤免疫治疗的新途径。
T cell immunity can potentially eradicate malignant cells and lead to clinical remission in a minority of patients with cancer. In the majority of these individuals, however, there is a failure of the specific T cell receptor (TCR)-mediated immune recognition and activation process. Here we describe the engineering and characterization of new reagents termed immune-mobilizing monoclonal TCRs against cancer (ImmTACs). Four such ImmTACs, each comprising a distinct tumor-associated epitope-specific monoclonal TCR with picomolar affinity fused to a humanized cluster of differentiation 3 (CD3)-specific single-chain antibody fragment (scFv), effectively redirected T cells to kill cancer cells expressing extremely low surface epitope densities. Furthermore, these reagents potently suppressed tumor growth in vivo. Thus, ImmTACs overcome immune tolerance to cancer and represent a new approach to tumor immunotherapy.