Immunocore Ltd., Abingdon, Oxon, UK.
Nat Med. 2012 Jun;18(6):980-7. doi: 10.1038/nm.2764.
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.
T 细胞免疫有可能消除恶性细胞，并导致少数癌症患者临床缓解。然而，在这些人中的大多数中，存在特定 T 细胞受体（TCR）介导的免疫识别和激活过程的失败。在这里，我们描述了新型试剂的工程设计和特性，这些试剂被称为针对癌症的免疫动员单克隆 TCR（ImmTACs）。这四种 ImmTAC 中的每一种都包含具有皮摩尔亲和力的独特肿瘤相关表位特异性单克隆 TCR，与人类化的分化簇 3（CD3）特异性单链抗体片段（scFv）融合，有效地将 T 细胞重新定向到杀伤表达极低表面表位密度的癌细胞。此外，这些试剂在体内有力地抑制了肿瘤生长。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方法。
