A tumor-localized approach to bypass anti-4-1BB immuno-toxicity

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. See related article by Hinner et al., p. xxx