Leland Stanford Junior University

Fred Hutchinson Cancer Center

Vincent Christopher Luca

Kenan Christopher Garcia

Irwin D Bernstein

R-spondin (RSPO) surrogate compositions and methods for their use are provided. RSPO surrogates of the invention comprise (i) a specific binding domain for Ring Finger Protein 43 (RNF43) or Zinc and Ring Finger Protein 3 (ZNRF3) and (ii) a cell targeting domain More specifically, wherein the specific binding domain for RNF43 or ZNRF3 is an antibody fragment, and wherein the cell targeting domain is a cytokine.

Compositions comprising R-Spondin (RSPO) surrogate molecules

This disclosure provides compositions and related methods providing targeted cell-specific inhibition of Notch receptor signaling. The disclosure provides a bi-specific molecule with separate domains that target the intended cell-type and the Notch receptor on that cell-type. The disclosure also provides for nucleic acids, vectors, and cells allowing for the expression of the bi-specific fusion molecules. The disclosure also provides related methods of making and using the bi-specific fusion molecule to inhibit Notch signaling in target cells of interest, including for the treatment of diseases characterized by a dysregulation of Notch signaling.

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Menlo Park, CA, United States of America

Vincent Christopher Luca