Fc-optimized anti-CD25 depletes tumor-infiltrating regulatory T cells and synergizes with PD-1 blockade to eradicate established tumors
Fc-optimized anti-CD25 depletes tumor-infiltrating regulatory T cells and synergizes with PD-1 blockade to eradicate established tumors
CD25 is expressed at high levels on regulatory T (Treg) cells and was initially proposed as a target for cancer immunotherapy. However, anti-CD25 antibodies have displayed limited activity against established tumors. We demonstrated that CD25 expression is largely restricted to tumor-infiltrating Treg cells in mice and humans. While existing anti-CD25 antibodies were observed to deplete Treg cells in the periphery, upregulation of the inhibitory Fc gamma receptor (FcγR) IIb at the tumor site prevented intra-tumoral Treg cell depletion, which may underlie the lack of anti-tumor activity previously observed in pre-clinical models. Use of an anti-CD25 antibody with enhanced binding to activating FcγRs led to effective depletion of tumor-infiltrating Treg cells, increased effector to Treg cell ratios, and improved control of established tumors. Combination with anti-programmed cell death protein-1 antibodies promoted complete tumor rejection, demonstrating the relevance of CD25 as a therapeutic target and promising substrate for future combination approaches in immune-oncology.
Journal Article
577-586
Arce Vargas, Frederick
893cc199-2be3-4fb7-8cfc-56c53ec784df
Furness, Andrew J.S.
0058746f-23f6-463d-94df-ccbb8d6513a2
Solomon, Isabelle
e48de986-589f-402c-907d-d3283df28cec
Joshi, Kroopa
48c0bcbb-88f7-405d-b5f3-4126ab80b67a
Mekkaoui, Leila
e6c623d9-791e-4ffe-a268-20b254a9f99a
Lesko, Marta H.
7fdb3a8a-f1b2-4c2a-9973-d855a8178f06
Miranda Rota, Enrique
b75d8115-1666-4b5c-994a-da70fc7c84fd
Dahan, Rony
ade40cab-36c3-4be0-908d-382af763e2d5
Georgiou, Andrew
72c5cebc-3ed4-4f5f-9e42-03a60fdcb6b1
Sledzinska, Anna
496be81a-5d6e-4a66-9ce4-a80fbd0df0f8
Ben Aissa, Assma
ee2800f2-9821-46af-9866-539d26b2bc7c
Franz, Dafne
14313fc7-f515-49e7-a82c-f6f1f5932a3a
Werner Sunderland, Mariana
444271cb-2a8d-435d-b409-d9f2ce6040b9
Wong, Yien Ning Sophia
b910e442-5fca-44c0-bea5-cac64645e8ee
Henry, Jake Y.
07fb0bda-0a15-4243-83a0-52eb55ab3722
O'Brien, Tim
c003b1d2-6299-4a79-9e3d-69fcb17675ac
Nicol, David
84146e01-40c5-4f32-976f-d1e30c8072a0
Challacombe, Ben
6ba79998-429f-4029-bb8e-551427fce9b3
Beers, Stephen A.
a02548be-3ffd-41ab-9db8-d6e8c3b499a2
Turajlic, Samra
20507bed-1bc2-46fc-b754-2c7622dc03a2
Gore, Martin
c38b4500-ccbd-4505-9c58-68c8b27b54f2
Larkin, James
00cc13b2-a896-4745-9664-732b26ec38ee
Swanton, Charles
ec4243a5-762e-4c4f-b05b-33759a19dce4
Chester, Kerry A
7d728478-f4e2-49b4-a66a-1ee531c1581a
Pule, Martin
b719ca80-b29a-47a7-8865-5035474e549d
Ravetch, Jeffrey V.
a28c47f0-099d-4129-87f6-addcf8465438
Marafioti, Teresa
2036b6e2-1157-4170-a533-a7c2307d619b
Peggs, Karl S.
a5c55130-46df-4945-9e55-ee15b2fd2f20
Quezada, Sergio A.
0f0f9dab-6569-472e-8bb3-39b63c989008
Melanoma TRACERx Consortium
18 April 2017
Arce Vargas, Frederick
893cc199-2be3-4fb7-8cfc-56c53ec784df
Furness, Andrew J.S.
0058746f-23f6-463d-94df-ccbb8d6513a2
Solomon, Isabelle
e48de986-589f-402c-907d-d3283df28cec
Joshi, Kroopa
48c0bcbb-88f7-405d-b5f3-4126ab80b67a
Mekkaoui, Leila
e6c623d9-791e-4ffe-a268-20b254a9f99a
Lesko, Marta H.
7fdb3a8a-f1b2-4c2a-9973-d855a8178f06
Miranda Rota, Enrique
b75d8115-1666-4b5c-994a-da70fc7c84fd
Dahan, Rony
ade40cab-36c3-4be0-908d-382af763e2d5
Georgiou, Andrew
72c5cebc-3ed4-4f5f-9e42-03a60fdcb6b1
Sledzinska, Anna
496be81a-5d6e-4a66-9ce4-a80fbd0df0f8
Ben Aissa, Assma
ee2800f2-9821-46af-9866-539d26b2bc7c
Franz, Dafne
14313fc7-f515-49e7-a82c-f6f1f5932a3a
Werner Sunderland, Mariana
444271cb-2a8d-435d-b409-d9f2ce6040b9
Wong, Yien Ning Sophia
b910e442-5fca-44c0-bea5-cac64645e8ee
Henry, Jake Y.
07fb0bda-0a15-4243-83a0-52eb55ab3722
O'Brien, Tim
c003b1d2-6299-4a79-9e3d-69fcb17675ac
Nicol, David
84146e01-40c5-4f32-976f-d1e30c8072a0
Challacombe, Ben
6ba79998-429f-4029-bb8e-551427fce9b3
Beers, Stephen A.
a02548be-3ffd-41ab-9db8-d6e8c3b499a2
Turajlic, Samra
20507bed-1bc2-46fc-b754-2c7622dc03a2
Gore, Martin
c38b4500-ccbd-4505-9c58-68c8b27b54f2
Larkin, James
00cc13b2-a896-4745-9664-732b26ec38ee
Swanton, Charles
ec4243a5-762e-4c4f-b05b-33759a19dce4
Chester, Kerry A
7d728478-f4e2-49b4-a66a-1ee531c1581a
Pule, Martin
b719ca80-b29a-47a7-8865-5035474e549d
Ravetch, Jeffrey V.
a28c47f0-099d-4129-87f6-addcf8465438
Marafioti, Teresa
2036b6e2-1157-4170-a533-a7c2307d619b
Peggs, Karl S.
a5c55130-46df-4945-9e55-ee15b2fd2f20
Quezada, Sergio A.
0f0f9dab-6569-472e-8bb3-39b63c989008