NKp46 binding proteins
Multispecific proteins that bind and specifically redirect NK cells to lyse a target cell of interest are provided without non-specific activation of NK cells in absence of target cells. The proteins have utility in the treatment of disease, notably cancer or infectious disease.
1. A recombinant monoclonal antibody or antigen-binding antibody fragment that specifically binds NKp46 comprising:
(a) a heavy chain variable region comprising CDRs 1, 2, and 3 of the heavy chain variable region of SEQ ID NO: 3 and a light chain variable region comprising CDRs 1, 2, and 3 of the light chain variable region of SEQ ID NO: 4;
(b) a heavy chain variable region comprising CDRs 1, 2 and 3 of the heavy chain variable region of SEQ ID NO: 5 and a light chain variable region comprising CDRs 1, 2, and 3 of the light chain variable region of SEQ ID NO: 6;
(c) a heavy chain variable region comprising CDRs 1, 2, and 3 of the heavy chain variable region of SEQ ID NO: 7 and a light chain variable region comprising CDRs 1, 2, and 3 of the light chain variable region of SEQ ID NO: 8;
(d) a heavy chain variable region comprising CDRs 1, 2, and 3 of the heavy chain variable region of SEQ ID NO: 9 and a light chain variable region comprising CDRs 1, 2, and 3 of the light chain variable region of SEQ ID NO: 10;
(e) a heavy chain variable region comprising CDRs 1, 2, and 3 of the heavy chain variable region of SEQ ID NO: 11 and a light chain variable region comprising CDRs 1, 2, and 3 of the light chain variable region of SEQ ID NO: 12; or
(f) a heavy chain variable region comprising CDRs 1, 2, and 3 of the heavy chain variable region of SEQ ID NO: 13 and a light chain variable region comprising CDRs 1, 2, and 3 of the light chain variable region of SEQ ID NO: 14.
2. A pharmaceutical composition comprising an antibody or antigen-binding antibody fragment according to claim 1 , and a pharmaceutically acceptable carrier.
3. The antibody of claim 1 , wherein the antibody or antibody fragment comprises a heavy chain variable region comprising CDRs 1, 2, and 3 of the heavy chain variable region of SEQ ID NO: 3 and a light chain variable region comprising CDRs 1, 2, and 3 of the light chain variable region of SEQ ID NO: 4.
4. The antibody of claim 1 , wherein the antibody or antibody fragment comprises a heavy chain variable region comprising CDRs 1, 2, and 3 of the heavy chain variable region of SEQ ID NO: 5 and a light chain variable region comprising CDRs 1, 2, and 3 of the light chain variable region of SEQ ID NO: 6.
5. The antibody of claim 1 , wherein the antibody or antibody fragment comprises a heavy chain variable region comprising CDRs 1, 2, and 3 of the heavy chain variable region of SEQ ID NO: 7 and a light chain variable region comprising CDRs 1, 2, and 3 of the light chain variable region of SEQ ID NO: 8.
6. The antibody of claim 1 , wherein the antibody or antibody fragment comprises a heavy chain variable region comprising CDRs 1, 2, and 3 of the heavy chain variable region of SEQ ID NO: 9 and a light chain variable region comprising CDRs 1, 2, and 3 of the light chain variable region of SEQ ID NO: 10.
7. The antibody of claim 1 , wherein the antibody or antibody fragment comprises a heavy chain variable region comprising CDRs 1, 2, and 3 of the heavy chain variable region of SEQ ID NO: 11 and a light chain variable region comprising CDRs 1, 2, and 3 of the light chain variable region of SEQ ID NO: 12.
8. The antibody of claim 1 , wherein the antibody or antibody fragment comprises a heavy chain variable region comprising CDRs 1, 2, and 3 of the heavy chain variable region of SEQ ID NO: 13 and a light chain variable region comprising CDRs 1, 2, and 3 of the light chain variable region of SEQ ID NO: 14.
9. The antibody of claim 1 , wherein the antibody or antibody fragment is a monospecific antibody.
10. A multispecific protein comprising any one of the antibody fragment of claim 1 .
11. A bispecific protein comprising any one of the antibody fragment of claim 1 .
12. A recombinant nucleic acid encoding an antibody or antigen-binding antibody fragment that specifically binds NKp46 comprising:
(a) a heavy chain variable region comprising CDRs 1, 2, and 3 of the heavy chain variable region of SEQ ID NO: 3 and a light chain variable region comprising CDRs 1, 2, and 3 of the light chain variable region of SEQ ID NO: 4;
(b) a heavy chain variable region comprising CDRs 1, 2, and 3 of the heavy chain variable region of SEQ ID NO: 5 and a light chain variable region comprising CDRs 1, 2, and 3 of the light chain variable region of SEQ ID NO: 6;
(c) a heavy chain variable region comprising CDRs 1, 2, and 3 of the heavy chain variable region of SEQ ID NO: 7 and a light chain variable region comprising CDRs 1, 2, and 3 of the light chain variable region of SEQ ID NO: 8;
(d) a heavy chain variable region comprising CDRs 1, 2, and 3 of the heavy chain variable region of SEQ ID NO: 9 and a light chain variable region comprising CDRs 1, 2, and 3 of the light chain variable region of SEQ ID NO: 10;
(e) a heavy chain variable region comprising CDRs 1, 2, and 3 of the heavy chain variable region of SEQ ID NO: 11 and a light chain variable region comprising CDRs 1, 2, and 3 of the light chain variable region of SEQ ID NO: 12; or
(f) a heavy chain variable region comprising CDRs 1, 2, and 3 of the heavy chain variable region of SEQ ID NO: 13 and a light chain variable region comprising CDRs 1, 2, and 3 of the light chain variable region of SEQ ID NO: 14.