CD45 sequestration lowers the signaling threshold in lymphocytes and enhances anti-tumor immunity.

ABSTRACT: CD45 plays a central role in immune signal regulation by controlling the spatial dynamics of phosphatase activity through steric segregation of its bulky rigid extracellular domain. To modulate CD45 activity, here we develop and characterize protein engineering approaches to induce multivalent clustering of CD45, effectively mimicking the endogenous local receptor sequestration during immune synapse formation. In doing so, we engineer a biologic that enables precise, tunable control over CD45 surface localization and activity. CD45 sequestration exhibited striking synergy when administered in combination with intratumorally anchored IL-12 therapy, markedly delaying tumor progression and extending survival in syngeneic murine melanoma and carcinoma models. Immune profiling revealed that CD8

SUBMITTER: Duhamel L 

PROVIDER: S-EPMC12324387 | biostudies-literature | 2025 Aug

REPOSITORIES: biostudies-literature