Cell Activation and Gene Expression Group, IBMC - Instituto de Biologia Molecular e Celular, Rua do Campo Alegre 823, 4150-180, Porto, Portugal.
BioDrugs. 2013 Jun;27(3):191-202. doi: 10.1007/s40259-013-0027-4.
The transmembrane surface glycoprotein CD6 was one of the first antigens identified on T lymphocytes. The recognition of its involvement in T-cell signaling processes heralds the potential of CD6 as a target for therapy in a number of pathologies associated with imbalances in T-cell function. Its tissue distribution, cellular expression, and overall molecular structure are well described, and the interaction with its physiological ligand CD166 has been determined to the amino-acid level. Nevertheless, the involvement of CD6 in signaling pathways remains poorly characterized and its biological function is controversial; still unresolved are whether CD6 is a co-stimulatory molecule in T-cell activation or, similar to the related CD5 antigen, a modulator of intracellular signaling. Here we revisit the earliest attempts of modulating immune function using CD6 monoclonal antibodies, and review the current thinking behind the recent developments in immunotherapy targeting CD6. Notwithstanding the promises and hopes brought by monoclonals already in clinical trials, the fact is that very little is known about the mechanism of action of these reagents, whether they enhance the physiological role of the receptor or whether they may induce a completely novel biochemical response that might, nevertheless, be beneficially used to treat human immune pathology.
跨膜表面糖蛋白 CD6 是最早在 T 淋巴细胞上鉴定出的抗原之一。其参与 T 细胞信号转导过程的识别预示着 CD6 作为治疗与 T 细胞功能失衡相关的多种病理学的靶点具有潜在可能性。其组织分布、细胞表达和整体分子结构已得到很好的描述，并且与生理配体 CD166 的相互作用已确定到氨基酸水平。然而，CD6 在信号转导途径中的参与仍未得到充分描述，其生物学功能也存在争议；尚未解决的问题是 CD6 是否是 T 细胞激活中的共刺激分子，或者是否类似于相关的 CD5 抗原，是细胞内信号转导的调节剂。在这里，我们重新审视了使用 CD6 单克隆抗体调节免疫功能的最早尝试，并回顾了针对 CD6 的免疫疗法的最新发展背后的当前思路。尽管已经在临床试验中使用的单克隆抗体带来了希望和承诺，但事实上，人们对这些试剂的作用机制知之甚少，无论是增强受体的生理作用，还是它们是否可能诱导一种全新的生化反应，而这种反应可能会被有益地用于治疗人类免疫病理学。
