Immunological reagents
This disclosure relates to binding agents with specificity for programmed cell death 1 (PD-1) and to methods for using the same to treat, prevent and/or ameliorate an infectious disease (e.g., human immunodeficiency virus (HIV)), cancer and/or autoimmunity. In addition, this disclosure identifies a novel binding patch (“P2”) on PD-1 that is linked with a previously unidentified functional activity of PD-1 that is distinct from the interaction site involved with either the PD-L1 or PD-L2 ligands. Furthermore, we demonstrate that antibodies that interact with this region of PD-1 are able to act as antagonists of PD-1 and that this antagonism is further enhanced with the addition of antibodies that act through the blockade of the PD-1/PD-L1/L2 interaction.
1. A binding agent that binds programmed cell death 1 (PD1) comprising the amino acid sequences of the heavy chain complementarity determining regions (CDRs) and light chain CDRs of antibodies 122F10, 139D6, 135D1, 121G1, 127C2, 132F7, 136E10, 135C12, 136F4, or 136B4.
2. The binding agent of claim 1 wherein the binding agent is an antibody.
3. The binding agent of claim 2 wherein the antibody is a mouse antibody.
4. The binding agent of claim 1 wherein the binding agent is selected from the group consisting of an F ab , F (ab′)2 , F ab′ , single chain antibody, F v , single domain antibody, mono-specific antibody, bi-specific antibody, tri-specific antibody, multi-valent antibody, chimeric antibody, canine-mouse chimeric antibody, antibody comprising a canine Fc, humanized antibody, caninized antibody, and CDR-grafted antibody.
5. The binding agent of claim 1 comprising a VH comprising complementarity determining regions (CDRs) 1, 2, and 3 as set forth in SEQ ID NOS: 17, 40, and 63, respectively; and a VL comprising CDRs 1, 2, and 3 as set forth in SEQ ID NOS: 86, 109, and 132, respectively.
6. A composition comprising the binding agent of claim 1 and at least one pharmaceutically acceptable carrier.
7. A composition comprising the binding agent of claim 2 and at least one pharmaceutically acceptable carrier.
8. A composition comprising the binding agent of claim 3 and at least one pharmaceutically acceptable carrier.
9. A composition comprising the binding agent of claim 4 and at least one pharmaceutically acceptable carrier.
10. A composition comprising the binding agent of claim 5 and at least one pharmaceutically acceptable carrier.
11. The composition of claim 6 further comprising pembrolizumab.
12. The composition of claim 7 further comprising pembrolizumab.
13. The composition of claim 8 further comprising pembrolizumab.
14. The composition of claim 9 further comprising pembrolizumab.
15. The composition of claim 10 further comprising pembrolizumab.