Compositions comprising R-Spondin (RSPO) surrogate molecules
View Patent ↗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.
1. An RSPO surrogate composition that comprises:
(i) a specific binding domain for RNF43 or ZNRF3, wherein the specific binding domain for RNF43 or ZNRF3 is an antibody or antigen-binding fragment thereof; and
(ii) a cell-targeting domain, wherein the cell-targeting domain is a cytokine or growth factor that specifically binds a cell surface receptor.
2. The composition of claim 1 , wherein the specific binding domain for RNF43 or ZNRF3 comprises 6 CDR sequences of Z6 or R5 binding sequences set forth in any one of SEQ ID NO:1-4.
3. The composition of claim 1 , wherein the specific binding domain for RNF43 or ZNRF3 is a single-chain Fv (scFv) construct.
4. The composition of claim 1 , wherein the cell-targeting domain is the or growth factor.
5. The composition of claim 4 , wherein the cell-targeting domain is the cytokine.
6. The composition of claim 5 , wherein the cytokine is IL-2 or IL-4.
7. The composition of claim 1 , wherein the domains are fused through a flexible linker.
8. The composition of claim 1 , wherein the domains are directly joined.
9. The composition of claim 1 , formulated with an effective dose of a Wnt agent.
10. The composition of claim 1 , joined to a Wnt agent.