Therapies based on control of regulatory t cell stability and function via a neuropilin-1:semaphorin axis

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.

1 . A method of inhibiting a function or decreasing stability of a regulatory T cell (Treg) comprising exposing said Treg to an inhibitor of neuropilin-1 (Nrp1):semaphorin axis in said Treg. 
     
     
         2 . The method of  claim 1 , wherein the inhibitor of Nrp1:semaphorin axis inhibits interaction between a transmembrane semaphorin on a cell expressing such transmembrane semaphorin and Nrp1 on the Treg. 
     
     
         3 - 6 . (canceled) 
     
     
         7 . The method of  claim 1 , wherein said Treg is in a subject and the inhibitor of Nrp1:semaphorin axis is administered to the subject. 
     
     
         8 . The method of  claim 7 , wherein the subject has a cancer. 
     
     
         9 - 12 . (canceled) 
     
     
         13 . The method of  claim 1 , wherein the inhibitor of Nrp1:semaphorin axis is an antibody. 
     
     
         14 - 47 . (canceled) 
     
     
         48 . A method of treating a disease in a subject in need thereof, the method comprising inhibiting neuropilin-1 (Nrp1):semaphorin axis in regulatory T cells (Tregs) of the subject. 
     
     
         49 . The method of  claim 48 , comprising inhibiting interaction between a transmembrane semaphorin on cells expressing such transmembrane semaphorin and Nrp1 on the Tregs of the subject. 
     
     
         50 - 51 . (canceled) 
     
     
         52 . The method of  claim 49 , wherein the cells expressing the transmembrane semaphorin are selected from the group consisting of conventional T cells (Tconv), conventional dendritic cells (cDCs), and plasmacytoid dendritic cells (pDCs). 
     
     
         53 . The method of  claim 48 , wherein the disease is a cancer. 
     
     
         54 - 57 . (canceled) 
     
     
         58 . The method of  claim 48 , comprising administering to the subject a therapeutically effective amount of an inhibitor of neuropilin-1 (Nrp1):semaphorin axis in Tregs of the subject. 
     
     
         59 . The method of  claim 58 , wherein the inhibitor of Nrp1:semaphorin axis is an antibody. 
     
     
         60 - 70 . (canceled) 
     
     
         71 . The method of  claim 58 , wherein the inhibitor of Nrp1:semaphorin axis prevents Nrp1 from engaging with its downstream signaling pathway(s). 
     
     
         72 . (canceled) 
     
     
         73 . The method of  claim 58 , further comprising administering to the subject an additional immunomodulatory treatment. 
     
     
         74 . The method of  claim 73 , wherein the additional immunomodulatory treatment comprises administering a therapeutic vaccine, a checkpoint inhibitor or an activator. 
     
     
         75 . The method of  claim 53 , further comprising administering to the subject a chemotherapy or a radiation therapy. 
     
     
         76 - 94 . (canceled) 
     
     
         95 . A method for enhancing the efficacy of a vaccine in a subject, the method comprising administering to the subject an effective amount of an inhibitor of neuropilin-1 (Nrp1):semaphorin axis in Tregs of the subject. 
     
     
         96 . The method of  claim 95 , wherein the inhibitor of Nrp1:semaphorin axis is an antibody. 
     
     
         97 - 110 . (canceled) 
     
     
         111 . The method of  claim 95 , wherein the vaccine is for treating or preventing cancer or infection. 
     
     
         112 - 116 . (canceled)