Tandem bispecific IL-7 receptor agonist antibody

Interleukin-7 (IL-7) is essential for T cell immunity, but the therapeutic application of existing IL-7 therapies is limited by narrow therapeutic window and suboptimal pharmacokinetics. To address this, we engineered a fully human tandem bispecific antibody, TB4, that functions as a potent IL-7 receptor (IL-7R) agonist by cross-linking the IL-7Rα and γc subunits. In primary human T cells, TB4 exhibited potent bispecific binding and induced sustained STAT5 signaling, a feature potentially associated with its slow antibody internalization rate. TB4 promoted T cell survival and the preferential expansion of CD4⁺ memory T cells. Notably, transcriptomic analysis revealed that TB4 induces a unique transcriptional signature enriched in genes associated with antiviral and innate immune responses, distinguishing it from native IL-7. These findings highlight TB4 as a promising IL-7R agonist with the potential to act as a subset-specific T cell immunomodulator, shaping both the expansion and functional profile of T cells.