Department of Immunobiology, Yale University School of Medicine, New Haven, Connecticut.
Department of Pathology, Yale University School of Medicine, New Haven, Connecticut.
Clin Cancer Res. 2019 Oct 1;25(19):5732-5734. doi: 10.1158/1078-0432.CCR-19-1799. Epub 2019 Jul 31.
4-1BB (CD137) is an important costimulatory molecule upregulated on antigen-experienced T cells, however, clinical development of 4-1BB agonists has stalled because of significant liver immuno-toxicity. Using rational protein engineering, a next-generation anticalin-antibody-based therapy achieved localized 4-1BB activation triggered by tumor-expressed antigen, helping to revitalize this pathway in immuno-oncology..
4-1BB（CD137）是一种在抗原经验性 T 细胞上上调的重要共刺激分子，然而，由于严重的肝脏免疫毒性，4-1BB 激动剂的临床开发已经停滞不前。通过合理的蛋白质工程，一种基于下一代抗钙蛋白抗体的治疗方法实现了肿瘤表达抗原触发的局部 4-1BB 激活，有助于使免疫肿瘤学中的这条途径重新焕发活力。
