US 12,747,296 B2 · Anti-CCR8 antibodies for treating cancer

Abstract

This disclosure provides isolated antibodies, for example, monoclonal antibodies, that specifically bind to the C-C Motif Chemokine Receptor 8 (CCR8) expressed on the surface of a cell and mediate depletion of the CCR8-expressing cell by anti-body-dependent cellular cytotoxicity (ADCC). The disclosure provides methods for treating a subject afflicted with a cancer comprising administering to the subject a therapeutically effective amount of an anti-CCR8 antibody as monotherapy or in combination with an anti-cancer agent such as an immune checkpoint inhibitor, for example, an anti-PD-1 or anti-PD-L1 antibody.

An anti-hCCR8 monoclonal antibody or an antigen-binding portion thereof which specifically binds to human C-C Motif Chemokine Receptor 8 (hCCR8, the sequence of which is set forth as SEQ ID NO:

1) expressed on the surface of an activated human regulatory T cell (Treg) with an EC50 of about 20 nM or lower as measured by a binding assay as described in Example 11 and mediates antibody-dependent cellular cytotoxicity (ADCC) killing of the activated human Treg, or a modified version of said anti-hCCR8 monoclonal antibody or an antigen-binding portion thereof which comprises a modified heavy chain constant region that binds with higher affinity to an Fcγ receptor and mediates enhanced ADCC compared to the unmodified anti-hCCR8 antibody, wherein the monoclonal antibody or the modified monoclonal antibody or the antigen-binding portion thereof comprises the following CDR domains as defined by the Kabat method:
(a) a heavy chain variable region CDR1 comprising consecutively linked amino acids having the sequence set forth as SEQ ID NO:
33;
a heavy chain variable region CDR2 comprising consecutively linked amino acids having the sequence set forth as SEQ ID NO:
34;
a heavy chain variable region CDR3 comprising consecutively linked amino acids having the sequence set forth as SEQ ID NO:
35;
a light chain variable region CDR1 comprising consecutively linked amino acids having the sequence set forth as SEQ ID NO:
36;
a light chain variable region CDR2 comprising consecutively linked amino acids having the sequence set forth as SEQ ID NO:
37;
and a light chain variable region CDR3 comprising consecutively linked amino acids having the sequence set forth as SEQ ID NO:
38;
(b) a heavy chain variable region CDR1 comprising consecutively linked amino acids having the sequence set forth as SEQ ID NO:
39;
a heavy chain variable region CDR2 comprising consecutively linked amino acids having the sequence set forth as SEQ ID NO:
40;
a heavy chain variable region CDR3 comprising consecutively linked amino acids having the sequence set forth as SEQ ID NO:
41;
a light chain variable region CDR1 comprising consecutively linked amino acids having the sequence set forth as SEQ ID NO:
42;
a light chain variable region CDR2 comprising consecutively linked amino acids having the sequence set forth as SEQ ID NO:
43;
and a light chain variable region CDR3 comprising consecutively linked amino acids having the sequence set forth as SEQ ID NO:
44;
(c) a heavy chain variable region CDR1 comprising consecutively linked amino acids having the sequence set forth as SEQ ID NO:
45;
a heavy chain variable region CDR2 comprising consecutively linked amino acids having the sequence set forth as SEQ ID NO:
46;
a heavy chain variable region CDR3 comprising consecutively linked amino acids having the sequence set forth as SEQ ID NO:
47;
a light chain variable region CDR1 comprising consecutively linked amino acids having the sequence set forth as SEQ ID NO:
48;
a light chain variable region CDR2 comprising consecutively linked amino acids having the sequence set forth as SEQ ID NO:
49;
and a light chain variable region CDR3 comprising consecutively linked amino acids having the sequence set forth as SEQ ID NO:
50;
(d) a heavy chain variable region CDR1 comprising consecutively linked amino acids having the sequence set forth as SEQ ID NO:
69;
a heavy chain variable region CDR2 comprising consecutively linked amino acids having the sequence set forth as SEQ ID NO:
70;
a heavy chain variable region CDR3 comprising consecutively linked amino acids having the sequence set forth as SEQ ID NO:
71;
a light chain variable region CDR1 comprising consecutively linked amino acids having the sequence set forth as SEQ ID NO:
72;
a light chain variable region CDR2 comprising consecutively linked amino acids having the sequence set forth as SEQ ID NO:
73;
and a light chain variable region CDR3 comprising consecutively linked amino acids having the sequence set forth as SEQ ID NO:
74;
(e) a heavy chain variable region CDR1 comprising consecutively linked amino acids having the sequence set forth as SEQ ID NO:
75;
a heavy chain variable region CDR2 comprising consecutively linked amino acids having the sequence set forth as SEQ ID NO:
76;
a heavy chain variable region CDR3 comprising consecutively linked amino acids having the sequence set forth as SEQ ID NO:
77;
a light chain variable region CDR1 comprising consecutively linked amino acids having the sequence set forth as SEQ ID NO:
78;
a light chain variable region CDR2 comprising consecutively linked amino acids having the sequence set forth as SEQ ID NO:
79;
and a light chain variable region CDR3 comprising consecutively linked amino acids having the sequence set forth as SEQ ID NO:
80;
or
(f) a heavy chain variable region CDR1 comprising consecutively linked amino acids having the sequence set forth as SEQ ID NO:
103;
a heavy chain variable region CDR2 comprising consecutively linked amino acids having the sequence set forth as SEQ ID NO:
104;
a heavy chain variable region CDR3 comprising consecutively linked amino acids having the sequence set forth as SEQ ID NO:
105;
a light chain variable region CDR1 comprising consecutively linked amino acids having the sequence set forth as SEQ ID NO:
106;
a light chain variable region CDR2 comprising consecutively linked amino acids having the sequence set forth as SEQ ID NO:
107;
and a light chain variable region CDR3 comprising consecutively linked amino acids having the sequence set forth as SEQ ID NO:
108.

71 more elements

Anti-CCR8 antibodies for treating cancer

Life of this patent

Anti-CCR8 antibodies for treating cancer

Life of this patent

Abstract

Claims36