THERAPIES BASED ON CONTROL OF REGULATORY T CELL STABILITY AND FUNCTION VIA A NEUROPILIN-1:SEMAPHORIN AXIS
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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.
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Citations
136 Claims
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1-116. -116. (canceled)
- 117. A pharmaceutical composition comprising an isolated anti-neuropilin-1 (NRP-1) antibody specific for cell surface NRP-1, wherein the anti-NRP-1 antibody is present in the composition in an amount effective to inhibit an interaction between NRP-1 and a transmembrane semaphorin-4 polypeptide when administered to a human subject.
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128. A method of inhibiting a function or decreasing stability of a regulatory T cell (Treg) comprising exposing the Treg in vivo to an inhibitor of neuropilin-1 (Nrp1):
- semaphorin-4 axis in the Treg, wherein the inhibitor comprises an anti-NRP-1 antibody.
- View Dependent Claims (129, 130, 131, 132, 133)
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134. A method of treating cancer in a human subject in need thereof, the method comprising the step of inhibiting a neuropilin-1 (Nrp1):
- semaphorin-4 axis in regulatory T cells (Tregs) of the subject, wherein the neuropilin-1 (Nrp1);
semaphorin-4 axis is inhibited by administration to the human subject of a pharmaceutical composition comprising an anti-NRP-1 antibody, thereby treating the cancer. - View Dependent Claims (135, 136)
- semaphorin-4 axis in regulatory T cells (Tregs) of the subject, wherein the neuropilin-1 (Nrp1);
Specification