Therapies based on control of regulatory T cell stability and function via a neuropilin-1:semaphorin axis
AssigneeSt. Jude Children's Research Hospital
InventorsDario A. A. Vignali, Seng-ryong Woo, Greg M. Delgoffe
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Abstract
The invention is directed to treatment of cancer, infections and various inflammatory and autoimmune conditions by affecting regulatory T cell stability and function via a Neuropilin-1:Semaphorin axis. The present invention satisfies this and other needs by demonstrating that the regulatory T cell (Treg)-restricted neuropilin-1 (Nrp 1) interacts with the cell surface ligand semaphorin-4a (Sema4a) (e.g., on conventional T cells (Tconv), conventional dendritic cells (cDCs), and/or plasmacytoid dendritic cells (pDCs)) to potentiate reg function and enhance their survival at inflammatory sites.
Claims16
A method of inhibiting a function or decreasing stability of a regulatory T cell (Treg) while maintaining immune homeostasis in a subject, comprising:
- exposing the Treg in vivo to an anti-neuropilin-1 (NRP-1) antibody or antigen-binding fragment thereof which inhibits a neuropilin-1 (Nrp1):
- semaphorin-4 axis, wherein the anti-NRP-1 antibody or antigen-binding fragment thereof inhibits interaction between i) a transmembrane semaphorin-4 polypeptide on a cell expressing the transmembrane semaphorin-4 and ii) a NRP-1 polypeptide on the Treg.
Dependencies are inferred from the claim text.