Methods and compositions for treating and preventing disease associated with alpha-v beta-8 integrin
Methods and compositions comprising integrin β8 antibodies are provided.
1. An isolated nucleic acid encoding an antibody that specifically binds to human integrin β8 and inhibits adhesion of latency associated peptide (LAP) to αvβ8, wherein the antibody comprises:
a heavy chain variable region comprising the Kabat-determined or Chothia-determined complementarity determining regions (HCDR1, HCDR2, and HCDR3) of SEQ ID NO:1 and a light chain variable region comprising the Kabat-determined or Chothia-determined complementarity determining regions (LCDR1, LCDR2, and LCDR3) of SEQ ID NO:16; or
a heavy chain variable region comprising the Kabat-determined or Chothia-determined complementarity determining regions (HCDR1, HCDR2, and HCDR3) of SEQ ID NO:2 and a light chain variable region comprising the Kabat-determined or Chothia-determined complementarity determining regions (LCDR1, LCDR2, and LCDR3) of SEQ ID NO:16; or
a heavy chain variable region comprising the Kabat-determined or Chothia-determined complementarity determining regions (HCDR1, HCDR2, and HCDR3) of SEQ ID NO:3 and a light chain variable region comprising the Kabat-determined or Chothia-determined complementarity determining regions (LCDR1, LCDR2, and LCDR3) of SEQ ID NO:16; or
a heavy chain variable region comprising the Kabat-determined or Chothia-determined complementarity determining regions (HCDR1, HCDR2, and HCDR3) of SEQ ID NO:4 and a light chain variable region comprising the Kabat-determined or Chothia-determined complementarity determining regions (LCDR1, LCDR2, and LCDR3) of SEQ ID NO:16; or
a heavy chain variable region comprising the Kabat-determined or Chothia-determined complementarity determining regions (HCDR1, HCDR2, and HCDR3) of SEQ ID NO:5 and a light chain variable region comprising the Kabat-determined or Chothia-determined complementarity determining regions (LCDR1, LCDR2, and LCDR3) of SEQ ID NO:16; or
a heavy chain variable region comprising the Kabat-determined or Chothia-determined complementarity determining regions (HCDR1, HCDR2, and HCDR3) of SEQ ID NO:6 and a light chain variable region comprising the Kabat-determined or Chothia-determined complementarity determining regions (LCDR1, LCDR2, and LCDR3) of SEQ ID NO:16; or
a heavy chain variable region comprising the Kabat-determined or Chothia-determined complementarity determining regions (HCDR1, HCDR2, and HCDR3) of SEQ ID NO:7 and a light chain variable region comprising the Kabat-determined or Chothia-determined complementarity determining regions (LCDR1, LCDR2, and LCDR3) of SEQ ID NO:17; or
a heavy chain variable region comprising the Kabat-determined or Chothia-determined complementarity determining regions (HCDR1, HCDR2, and HCDR3) of SEQ ID NO:8 and a light chain variable region comprising the Kabat-determined or Chothia-determined complementarity determining regions (LCDR1, LCDR2, and LCDR3) of SEQ ID NO:18; or
a heavy chain variable region comprising the Kabat-determined or Chothia-determined complementarity determining regions (HCDR1, HCDR2, and HCDR3) of SEQ ID NO:9 and a light chain variable region comprising the Kabat-determined or Chothia-determined complementarity determining regions (LCDR1, LCDR2, and LCDR3) of SEQ ID NO:19; or
a heavy chain variable region comprising the Kabat-determined or Chothia-determined complementarity determining regions (HCDR1, HCDR2, and HCDR3) of SEQ ID NO:10 and a light chain variable region comprising the Kabat-determined or Chothia-determined complementarity determining regions (LCDR1, LCDR2, and LCDR3) of SEQ ID NO:20; or
a heavy chain variable region comprising the Kabat-determined or Chothia-determined complementarity determining regions (HCDR1, HCDR2, and HCDR3) of SEQ ID NO:11 and a light chain variable region comprising the Kabat-determined or Chothia-determined complementarity determining regions (LCDR1, LCDR2, and LCDR3) of SEQ ID NO:20; or
a heavy chain variable region comprising the Kabat-determined or Chothia-determined complementarity determining regions (HCDR1, HCDR2, and HCDR3) of SEQ ID NO:12 and a light chain variable region comprising the Kabat-determined or Chothia-determined complementarity determining regions (LCDR1, LCDR2, and LCDR3) of SEQ ID NO:20; or
a heavy chain variable region comprising the Kabat-determined or Chothia-determined complementarity determining regions (HCDR1, HCDR2, and HCDR3) of SEQ ID NO:13 and a light chain variable region comprising the Kabat-determined or Chothia-determined complementarity determining regions (LCDR1, LCDR2, and LCDR3) of SEQ ID NO:20; or
a heavy chain variable region comprising the Kabat-determined or Chothia-determined complementarity determining regions (HCDR1, HCDR2, and HCDR3) of SEQ ID NO:14 and a light chain variable region comprising the Kabat-determined or Chothia-determined complementarity determining regions (LCDR1, LCDR2, and LCDR3) of SEQ ID NO:21; or
a heavy chain variable region comprising the Kabat-determined or Chothia-determined complementarity determining regions (HCDR1, HCDR2, and HCDR3) of SEQ ID NO:15 and a light chain variable region comprising the complementarity determining regions (LCDR1, LCDR2, and LCDR3) of SEQ ID NO:22.
2. The isolated nucleic acid of claim 1 , wherein the antibody comprises one or more human framework regions.
3. The isolated nucleic acid of claim 1 , wherein
HCDR1 comprises SEQ ID NO:88, HCDR2 comprises SEQ ID NO:90, and HCDR3 comprises SEQ ID NO:25, and
LCDR1 comprises SEQ ID NO:46, LCDR2 comprises SEQ ID NO:47, and LCDR3 comprises SEQ ID NO:48.
4. The isolated nucleic acid of claim 1 , wherein
HCDR1 comprises SEQ ID NO:89, HCDR2 comprises SEQ ID NO:24, and HCDR3 comprises SEQ ID NO:25, and
LCDR1 comprises SEQ ID NO:46, LCDR2 comprises SEQ ID NO:47, and LCDR3 comprises SEQ ID NO:48.
5. The isolated nucleic acid of claim 1 , wherein
HCDR1 comprises SEQ ID NO:89, HCDR2 comprises SEQ ID NO:26, and HCDR3 comprises SEQ ID NO:25, and
LCDR1 comprises SEQ ID NO:46, LCDR2 comprises SEQ ID NO:47, and LCDR3 comprises SEQ ID NO:48.
6. The isolated nucleic acid of claim 1 , wherein
HCDR1 comprises SEQ ID NO:91, HCDR2 comprises SEQ ID NO:93, and HCDR3 comprises SEQ ID NO:29, and
LCDR1 comprises SEQ ID NO:46, LCDR2 comprises SEQ ID NO:49, and LCDR3 comprises SEQ ID NO:50.
7. The isolated nucleic acid of claim 1 , wherein HCDR1 comprises SEQ ID NO:92, HCDR2 comprises SEQ ID NO:28, and HCDR3 comprises SEQ ID NO:29, and
LCDR1 comprises SEQ ID NO:46, LCDR2 comprises SEQ ID NO:49, and LCDR3 comprises SEQ ID NO:50.
8. The isolated nucleic acid of claim 1 , wherein HCDR1 comprises SEQ ID NO:94, HCDR2 comprises SEQ ID NO:96, and HCDR3 comprises SEQ ID NO:32, and
LCDR1 comprises SEQ ID NO:51, LCDR2 comprises SEQ ID NO:52, and LCDR3 comprises SEQ ID NO:53.
9. The isolated nucleic acid of claim 1 , wherein
HCDR1 comprises SEQ ID NO:95, HCDR2 comprises SEQ ID NO:31, and HCDR3 comprises SEQ ID NO:32, and
LCDR1 comprises SEQ ID NO:51, LCDR2 comprises SEQ ID NO:52, and LCDR3 comprises SEQ ID NO:53.
10. The isolated nucleic acid of claim 1 , wherein
HCDR1 comprises SEQ ID NO:97, HCDR2 comprises SEQ ID NO:99, and HCDR3 comprises SEQ ID NO:35, and
LCDR1 comprises SEQ ID NO:54, LCDR2 comprises SEQ ID NO:55, and LCDR3 comprises SEQ ID NO:56.
11. The isolated nucleic acid of claim 1 , wherein
HCDR1 comprises SEQ ID NO:98, HCDR2 comprises SEQ ID NO:34, and HCDR3 comprises SEQ ID NO:35, and
LCDR1 comprises SEQ ID NO:54, LCDR2 comprises SEQ ID NO:55, and LCDR3 comprises SEQ ID NO:56.
12. The isolated nucleic acid of claim 1 , wherein
HCDR1 comprises SEQ ID NO:100, HCDR2 comprises SEQ ID NO:102, and HCDR3 comprises SEQ ID NO:38, and
LCDR1 comprises SEQ ID NO:57, LCDR2 comprises SEQ ID NO:58, and LCDR3 comprises SEQ ID NO:59.
13. The isolated nucleic acid of claim 1 , wherein
HCDR1 comprises SEQ ID NO:101, HCDR2 comprises SEQ ID NO:37, and HCDR3 comprises SEQ ID NO:38, and
LCDR1 comprises SEQ ID NO:57, LCDR2 comprises SEQ ID NO:58, and LCDR3 comprises SEQ ID NO:59.
14. The isolated nucleic acid of claim 1 , wherein
HCDR1 comprises SEQ ID NO:101, HCDR2 comprises SEQ ID NO:39, and HCDR3 comprises SEQ ID NO:38, and
LCDR1 comprises SEQ ID NO:57, LCDR2 comprises SEQ ID NO:58, and LCDR3 comprises SEQ ID NO:59.
15. The isolated nucleic acid of claim 1 , wherein
HCDR1 comprises SEQ ID NO:103, HCDR2 comprises SEQ ID NO:105, and HCDR3 comprises SEQ ID NO:42, and
LCDR1 comprises SEQ ID NO:60, LCDR2 comprises SEQ ID NO:61, and LCDR3 comprises SEQ ID NO:62.
16. The isolated nucleic acid of claim 1 , wherein
HCDR1 comprises SEQ ID NO:104, HCDR2 comprises SEQ ID NO:41, and HCDR3 comprises SEQ ID NO:42, and
LCDR1 comprises SEQ ID NO:60, LCDR2 comprises SEQ ID NO:61, and LCDR3 comprises SEQ ID NO:62.
17. The isolated nucleic acid of claim 1 , wherein
HCDR1 comprises SEQ ID NO:106, HCDR2 comprises SEQ ID NO:108, and HCDR3 comprises SEQ ID NO:45, and
LCDR1 comprises SEQ ID NO:63, LCDR2 comprises SEQ ID NO:64, and LCDR3 comprises SEQ ID NO:65.
18. The isolated nucleic acid of claim 1 , wherein
HCDR1 comprises SEQ ID NO:107, HCDR2 comprises SEQ ID NO:44, and HCDR3 comprises SEQ ID NO:45, and
LCDR1 comprises SEQ ID NO:63, LCDR2 comprises SEQ ID NO:64, and LCDR3 comprises SEQ ID NO:65.
19. The isolated nucleic acid of claim 1 , wherein the nucleic acid comprises any of SEQ ID NOS: 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, or 87.
20. An expression vector comprising the nucleic acid of claim 1 .
21. An isolated host cell comprising the vector of claim 19 .