TL1A (TNFSF15) is a TNF superfamily ligand which can bind the TNFRSF member death receptor 3 (DR3) on T cells and the soluble decoy receptor DcR3. Engagement of DR3 on CD4+ or CD8+ effector T cells by TL1A induces downstream signaling, leading to proliferation and an increase in secretion of inflammatory cytokines. We designed a stable recombinant TL1A molecule that (1) displays high monodispersity and stability, (2) displays the ability to activate T cells in vitro and in vivo, and (3) lacks binding to DcR3 while retaining functional activity via DR3. Together these results suggest the TL1A ligand can be amenable to therapeutic development on its own or paired with a tumor-targeting moiety.

TL1A (TNFSF15) 是一种 TNF 超家族配体，可结合 T 细胞上的 TNFRSF 成员死亡受体 3 (DR3) 和可溶性诱饵受体 DcR3。TL1A 使 DR3 与 CD4+ 或 CD8+ 效应 T 细胞结合，诱导下游信号传导，导致增殖和炎性细胞因子分泌增加。我们设计了一种稳定的重组 TL1A 分子，它 (1) 显示出高单分散性和稳定性，(2) 显示出在体外和体内激活 T 细胞的能力，以及 (3) 缺乏与 DcR3 的结合，同时通过 DR3 保留功能活性。这些结果共同表明，TL1A 配体可以单独进行治疗开发或与肿瘤靶向部分配对。