Modular cytokine receptor-targeting chimeras for targeted degradation of cell surface and extracellular proteins

Targeted degradation of cell surface and extracellular proteins via lysosomal delivery is an important means to modulate extracellular biology. However, these approaches have limitations due to lack of modularity, ease of development, restricted tissue targeting and applicability to both cell surface and extracellular proteins. We describe a lysosomal degradation strategy, termed cytokine receptor-targeting chimeras (KineTACs), that addresses these limitations. KineTACs are fully genetically encoded bispecific antibodies consisting of a cytokine arm, which binds its cognate cytokine receptor, and a target-binding arm for the protein of interest. We show that KineTACs containing the cytokine CXCL12 can use the…

• NI
  National Institutes of Health

  Award: R35GM122451
• UO
  University of California, San Francisco
• NC
  National Cancer Institute

  Awards: 5F32CA239417, 1F31CA265080-01, R01CA248323