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Engineered IgA Antibody Enters Kidney Cysts, Dampens PKD Growth Signals in Mice

UCSB researchers report preclinical results in Cell Reports Medicine with further development required before human testing.

Overview

  • In mouse models, a dimeric IgA monoclonal antibody traversed epithelial layers into kidney cysts by engaging polymeric immunoglobulin receptors.
  • The antibody antagonized the cMET receptor, reducing downstream growth signaling implicated in polycystic kidney disease progression.
  • Treatment triggered apoptosis in cyst-lining cells while sparing healthy renal tissue, with no apparent deleterious effects reported.
  • The team converted an IgG backbone into a dIgA format through DNA sequence engineering, verified target engagement in vitro, and observed cyst entry and retention in vivo.
  • Authors highlight the need to compare additional growth-factor targets, explore antibody combinations, and secure partners and manufacturing capacity, noting NIH and U.S. Department of Defense support.