ANTI-CD94 ANTIBODIES AND METHODS OF USE THEREOF
The present disclosure relates to antibodies that bind to human CD94, as well as methods, uses, polynucleotides, vectors, host cells, and pharmaceutical compositions related thereto. In some embodiments, the antibodies are human or humanized antibodies that bind to human CD94 and do not block binding between CD94 and HLA-E. In some embodiments, the antibodies cross-react with cynomolgus CD94. In some embodiments, the antibodies do not promote internalization of surface-expressed CD94 to the extent of existing antibodies. In some embodiments, the antibodies promote ADCC targeting cells that express human CD94, e.g., on the cell surface.
1 - 10 . (canceled)
11 . An antibody that binds to human CD94, wherein the antibody comprises a heavy chain variable (VH) domain and a light chain variable (VL) domain, wherein:
(a) the VH domain comprises a CDR-H1 comprising the amino acid sequence of SEQ ID NO: 1, a CDR-H2 comprising the amino acid sequence of SEQ ID NO:2, and a CDR-H3 comprising the amino acid sequence of SEQ ID NO:3; and the VL domain comprises a CDR-L1 comprising the amino acid sequence of SEQ ID NO:4, a CDR-L2 comprising the amino acid sequence of SEQ ID NO:5, and a CDR-L3 comprising the amino acid sequence of SEQ ID NO:6;
(b) the VH domain comprises a CDR-H1 comprising the amino acid sequence of SEQ ID NO:7, a CDR-H2 comprising the amino acid sequence of SEQ ID NO:8, and a CDR-H3 comprising the amino acid sequence of SEQ ID NO:9; and the VL domain comprises a CDR-L1 comprising the amino acid sequence of SEQ ID NO: 10, a CDR-L2 comprising the amino acid sequence of SEQ ID NO: 11, and a CDR-L3 comprising the amino acid sequence of SEQ ID NO:12;
(c) the VH domain comprises a CDR-H1 comprising the amino acid sequence of SEQ ID NO: 13, a CDR-H2 comprising the amino acid sequence of SEQ ID NO: 14, and a CDR-H3 comprising the amino acid sequence of SEQ ID NO: 15; and the VL domain comprises a CDR-L1 comprising the amino acid sequence of SEQ ID NO: 16, a CDR-L2 comprising the amino acid sequence of SEQ ID NO: 17, and a CDR-L3 comprising the amino acid sequence of SEQ ID NO:18;
(d) the VH domain comprises a CDR-H1 comprising the amino acid sequence of SEQ ID NO:30, a CDR-H2 comprising the amino acid sequence of SEQ ID NO:31, and a CDR-H3 comprising the amino acid sequence of SEQ ID NO:32; and the VL domain comprises a CDR-L1 comprising the amino acid sequence of SEQ ID NO:33, a CDR-L2 comprising the amino acid sequence of SEQ ID NO:34, and a CDR-L3 comprising the amino acid sequence of SEQ ID NO:35;
(e) the VH domain comprises a CDR-H1 comprising the amino acid sequence of SEQ ID NO:36, a CDR-H2 comprising the amino acid sequence of SEQ ID NO:39, and a CDR-H3 comprising the amino acid sequence of SEQ ID NO:40; and the VL domain comprises a CDR-L1 comprising the amino acid sequence of SEQ ID NO:33, a CDR-L2 comprising the amino acid sequence of SEQ ID NO:34, and a CDR-L3 comprising the amino acid sequence of SEQ ID NO:35;
(f) the VH domain comprises a CDR-H1 comprising the amino acid sequence of SEQ ID NO:41, a CDR-H2 comprising the amino acid sequence of SEQ ID NO:42, and a CDR-H3 comprising the amino acid sequence of SEQ ID NO:43; and the VL domain comprises a CDR-L1 comprising the amino acid sequence of SEQ ID NO:44, a CDR-L2 comprising the amino acid sequence of SEQ ID NO:45, and a CDR-L3 comprising the amino acid sequence of SEQ ID NO:46;
(g) the VH domain comprises a CDR-H1 comprising the amino acid sequence of SEQ ID NO:47, a CDR-H2 comprising the amino acid sequence of SEQ ID NO:48, and a CDR-H3 comprising the amino acid sequence of SEQ ID NO:49; and the VL domain comprises a CDR-L1 comprising the amino acid sequence of SEQ ID NO:50, a CDR-L2 comprising the amino acid sequence of SEQ ID NO:51, and a CDR-L3 comprising the amino acid sequence of SEQ ID NO:52;
(h) the VH domain comprises a CDR-H1 comprising the amino acid sequence of SEQ ID NO:57, a CDR-H2 comprising the amino acid sequence of SEQ ID NO:58, and a CDR-H3 comprising the amino acid sequence of SEQ ID NO:59; and the VL domain comprises a CDR-L1 comprising the amino acid sequence of SEQ ID NO:60, a CDR-L2 comprising the amino acid sequence of SEQ ID NO:34, and a CDR-L3 comprising the amino acid sequence of SEQ ID NO:61;
(i) the VH domain comprises a CDR-H1 comprising the amino acid sequence of SEQ ID NO:36, a CDR-H2 comprising the amino acid sequence of SEQ ID NO:37, and a CDR-H3 comprising the amino acid sequence of SEQ ID NO:38; and the VL domain comprises a CDR-L1 comprising the amino acid sequence of SEQ ID NO:33, a CDR-L2 comprising the amino acid sequence of SEQ ID NO:34, and a CDR-L3 comprising the amino acid sequence of SEQ ID NO:35;
(j) the VH domain comprises a CDR-H1 comprising the amino acid sequence of SEQ ID NO:53, a CDR-H2 comprising the amino acid sequence of SEQ ID NO:54, and a CDR-H3 comprising the amino acid sequence of SEQ ID NO:55; and the VL domain comprises a CDR-L1 comprising the amino acid sequence of SEQ ID NO:50, a CDR-L2 comprising the amino acid sequence of SEQ ID NO:45, and a CDR-L3 comprising the amino acid sequence of SEQ ID NO:56; or
(k) the VH domain comprises a CDR-H1 comprising the amino acid sequence of SEQ ID NO:83, a CDR-H2 comprising the amino acid sequence of SEQ ID NO:84, and a CDR-H3 comprising the amino acid sequence of SEQ ID NO:85; and wherein the VL domain comprises a CDR-L1 comprising the amino acid sequence of SEQ ID NO:86, a CDR-L2 comprising the amino acid sequence of SEQ ID NO:34, and a CDR-L3 comprising the amino acid sequence of SEQ ID NO:61.
12 . The antibody of claim 11 , wherein:
(a) the VH domain comprises an amino acid sequence with at least 80% sequence identity to the amino acid sequence of SEQ ID NO: 19, and the VL domain comprises an amino acid sequence with at least 80% sequence identity to the amino acid sequence of SEQ ID NO:20;
(b) the VH domain comprises an amino acid sequence with at least 80% sequence identity to the amino acid sequence of SEQ ID NO:21, and the VL domain comprises an amino acid sequence with at least 80% sequence identity to the amino acid sequence of SEQ ID NO:22;
(c) the VH domain comprises an amino acid sequence with at least 80% sequence identity to the amino acid sequence of SEQ ID NO:23, and the VL domain comprises an amino acid sequence with at least 80% sequence identity to the amino acid sequence of SEQ ID NO:24;
(d) the VH domain comprises an amino acid sequence with at least 80% sequence identity to the amino acid sequence of SEQ ID NO:65, and the VL domain comprises an amino acid sequence with at least 80% sequence identity to the amino acid sequence of SEQ ID NO:66;
(e) the VH domain comprises an amino acid sequence with at least 80% sequence identity to the amino acid sequence of SEQ ID NO:69, and the VL domain comprises an amino acid sequence with at least 80% sequence identity to the amino acid sequence of SEQ ID NO:70;
(f) the VH domain comprises an amino acid sequence with at least 80% sequence identity to the amino acid sequence of SEQ ID NO:71, and the VL domain comprises an amino acid sequence with at least 80% sequence identity to the amino acid sequence of SEQ ID NO:72;
(g) the VH domain comprises an amino acid sequence with at least 80% sequence identity to the amino acid sequence of SEQ ID NO:73, and the VL domain comprises an amino acid sequence with at least 80% sequence identity to the amino acid sequence of SEQ ID NO:74;
(h) the VH domain comprises an amino acid sequence with at least 80% sequence identity to the amino acid sequence of SEQ ID NO:77, and the VL domain comprises an amino acid sequence with at least 80% sequence identity to the amino acid sequence of SEQ ID NO:78;
(i) the VH domain comprises an amino acid sequence with at least 80% sequence identity to the amino acid sequence of SEQ ID NO:67, and the VL domain comprises an amino acid sequence with at least 80% sequence identity to the amino acid sequence of SEQ ID NO:68;
(j) the VH domain comprises an amino acid sequence with at least 80% sequence identity to the amino acid sequence of SEQ ID NO:75, and the VL domain comprises an amino acid sequence with at least 80% sequence identity to the amino acid sequence of SEQ ID NO:76; or
(k) the VH domain comprises an amino acid sequence with at least 80% sequence identity to the amino acid sequence of SEQ ID NO:79, and the VL domain comprises an amino acid sequence with at least 80% sequence identity to the amino acid sequence of SEQ ID NO:80.
13 . The antibody of claim 12 , wherein:
(a) the VH domain comprises the amino acid sequence of SEQ ID NO: 19, and the VL domain comprises the amino acid sequence of SEQ ID NO:20;
(b) the VH domain comprises the amino acid sequence of SEQ ID NO:21, and the VL domain comprises the amino acid sequence of SEQ ID NO:22;
(c) the VH domain comprises the amino acid sequence of SEQ ID NO:23, and the VL domain comprises the amino acid sequence of SEQ ID NO:24;
(d) the VH domain comprises the amino acid sequence of SEQ ID NO:65, and the VL domain comprises the amino acid sequence of SEQ ID NO:66;
(e) the VH domain comprises the amino acid sequence of SEQ ID NO:69, and the VL domain comprises the amino acid sequence of SEQ ID NO:70;
(f) the VH domain comprises the amino acid sequence of SEQ ID NO:71, and the VL domain comprises the amino acid sequence of SEQ ID NO:72;
(g) the VH domain comprises the amino acid sequence of SEQ ID NO:73, and the VL domain comprises the amino acid sequence of SEQ ID NO:74;
(h) the VH domain comprises the amino acid sequence of SEQ ID NO:77, and the VL domain comprises the amino acid sequence of SEQ ID NO:78;
(i) the VH domain comprises the amino acid sequence of SEQ ID NO:67, and the VL domain comprises the amino acid sequence of SEQ ID NO:68;
(j) the VH domain comprises the amino acid sequence of SEQ ID NO:75, and the VL domain comprises the amino acid sequence of SEQ ID NO:76; or
(k) the VH domain comprises the amino acid sequence of SEQ ID NO:79, and the VL domain comprises the amino acid sequence of SEQ ID NO:80.
14 - 52 . (canceled)
53 . The antibody of claim 11 , wherein the antibody is an antigen-binding antibody fragment or single chain antibody.
54 . The antibody of claim 11 , wherein the antibody further comprises an Fc region.
55 . The antibody of claim 54 , wherein the Fc region is a human IgG1 Fc region.
56 . The antibody of claim 54 , wherein the antibody comprises a human Fc region that is non-fucosylated.
57 - 58 . (canceled)
59 . A polynucleotide encoding the antibody of claim 11 .
60 . A vector comprising the polynucleotide of claim 59 .
61 . (canceled)
62 . An isolated host cell comprising the polynucleotide of claim 59 .
63 . A method of producing an antibody, comprising culturing the host cell of claim 62 under conditions suitable for production of the antibody.
64 . (canceled)
65 . A pharmaceutical composition comprising the antibody of claim 11 and a pharmaceutically acceptable carrier.
66 . A method for treating a disease or disorder in a subject, comprising administering to the subject an effective amount of the antibody of claim 11 .
67 - 75 . (canceled)
76 . A method for reducing the number of peripheral blood LGL and/or NK cells in a subject, comprising administering to the subject an effective amount of the antibody of claim 11 .
77 . A method for inducing ADCC activity in a subject, comprising administering to the subject an effective amount of the antibody of claim 11 .
78 . A method for treating CLPD-NK in a human subject in need thereof, comprising administering to the subject an effective amount of the antibody of claim 11 .
79 - 84 . (canceled)
85 . A method for enhancing chimeric antigen receptor T cell (CAR-T) therapy in a human subject in need thereof, comprising administering to the subject an effective amount of the antibody of claim 11 prior to administration of a CAR-T treatment to the subject.
86 . (canceled)
87 . A method for depleting CD8+ CD94+ T cells in a human subject in need thereof, comprising administering to the subject an effective amount of the antibody of claim 11 .
88 . (canceled)
89 . The method of claim 66 , wherein the subject is a human.