Antibodies that bind integrin AVB8 and uses thereof
Antibodies that bind to ανβ8 are provided.
1. An antibody that specifically binds human ανβ8, wherein the antibody comprises:
a heavy chain complementary determining region (HCDR) 1 comprising TFTDYSMH (SEQ ID NO:1) or TFTKYSMH (SEQ ID NO:2);
a HCDR 2 comprising RINTETGEPTFADDFRG (SEQ ID NO:3);
a HCDR 3 comprising FYYGRD(S/T) (SEQ ID NO:4);
a light chain complementary determining region (LCDR) 1 comprising KSSQSLLNSRSRKNYLA (SEQ ID NO:5) or KSSQSLLHSRSRKNYLA (SEQ ID NO:6);
a LCDR2 comprising WASTRES (SEQ ID NO:7); and
a LCDR3 comprising KQSYNLLS (SEQ ID NO:8), wherein the antibody comprises one or none of SEQ ID NO:1 and SEQ ID NO:5, but not both of SEQ ID NO:1 and SEQ ID NO:5.
2. The antibody of claim 1 , wherein the HCDR1 comprises SEQ ID NO:2 and the LCDR1 comprises SEQ ID NO:6.
3. The antibody of claim 1 , wherein the HCDR1 comprises SEQ ID NO:1 and the LCDR1 comprises SEQ ID NO:6.
4. The antibody of claim 1 , wherein the HCDR1 comprises SEQ ID NO:2 and the LCDR1 comprises SEQ ID NO:5.
5. The antibody of claim 1 , comprising a heavy chain variable region comprising SEQ ID NO:9.
6. The antibody of claim 1 , comprising a light chain variable region comprising SEQ ID NO: 10.
7. The antibody of claim 1 , wherein the antibody is humanized.
8. The antibody of claim 1 , wherein the antibody is linked to a detectable label.
9. An antibody that binds human ανβ8 and ανβ6, wherein the antibody comprises:
a heavy chain complementary determining region (HCDR) 1 comprising TFTDYSMH (SEQ ID NO:1) or TFTKYSMH (SEQ ID NO:2);
a HCDR 2 comprising RINTETGEPTFADDFRG (SEQ ID NO:3);
a HCDR 3 comprising FYYGRD(S/T) (SEQ ID NO:4);
a light chain complementary determining region (LCDR) 1 comprising KSSQSLLRRGDLATIHGNALA (SEQ ID NO:11);
a LCDR2 comprising WASTRES (SEQ ID NO:7); and
a LCDR3 comprising KQSYNLLS (SEQ ID NO:8); or
wherein the antibody comprises:
a heavy chain complementary determining region (HCDR) 1 comprising TFTKYSMH (SEQ ID NO:2);
a HCDR 2 comprising RINTETGEPTFADDFRG (SEQ ID NO:3);
a HCDR 3 comprising FYYGRD(S/T) (SEQ ID NO:4);
a light chain complementary determining region (LCDR) 1 comprising a sequence selected from the group consisting of SEQ ID NO:40, SEQ ID NO:41, SEQ ID NO:42, SEQ ID NO:43, SEQ ID NO:44, SEQ ID NO:45, SEQ ID NO:46, SEQ ID NO:47, SEQ ID NO:48, SEQ ID NO:49, SEQ ID NO:50, SEQ ID NO:51, SEQ ID NO:52, SEQ ID NO:53, SEQ ID NO:54, SEQ ID NO:55, SEQ ID NO:56, SEQ ID NO:57, SEQ ID NO:58, and SEQ ID NO:59;
a LCDR2 comprising WASTRES (SEQ ID NO:7); and
a LCDR3 comprising KQSYNLLS (SEQ ID NO:8).
10. The antibody of claim 9 , comprising a heavy chain variable region comprising SEQ ID NO:9.
11. The antibody of claim 9 , comprising a light chain variable region comprising SEQ ID NO:12.
12. The antibody of claim 9 , wherein the antibody is humanized.
13. The antibody of claim 9 , wherein the antibody is linked to a detectable label.
14. The antibody of claim 9 , wherein the HCDR1 comprises SEQ ID NO:2 and the LCDR1 comprises SEQ ID NO:40.
15. The antibody of claim 9 , comprising a light chain variable region comprising SEQ ID NO:39.
16. A method of enhancing an immune response to cancer or a viral infection in a human individual, the method comprising administering a sufficient amount of the antibody of claim 1 to the individual, thereby enhancing an immune response to the cancer or the viral infection.
17. The method of claim 16 , wherein the cancer is lung cancer.
18. The method of claim 16 , wherein the cancer is a metastatic cancer.
19. The method of claim 16 , wherein the cancer is a primary cancer.