Methods of using anti-TREM2 antibodies
Provided herein are anti-TREM2 antibodies and related methods of making and using anti-TREM2 antibodies. Also provided are methods and compositions for enhancing an immune response and/or for the treatment of an immune-related condition in an individual, e.g., cancer, using an anti-TREM2 antibody or antigen binding fragment thereof.
1 . A method of treating ovarian cancer in a subject in need thereof, comprising administering to the subject an isolated anti-TREM2 antibody comprising a variable heavy domain (VH) sequence comprising a CDR-H1, a CDR-H2, and a CDR-H3 and a variable light domain (VL) sequence comprising a CDR-L1, a CDR-L2, and a CDR-L3, and wherein:
a. the CDR-H1 comprises the sequence set forth in SEQ ID NO: 9 or 39,
b. the CDR-H2 comprises the sequence set forth in SEQ ID NO: 10 or 40,
c. the CDR-H3 comprises the sequence set forth in SEQ ID NO: 11 or 41,
d. the CDR-L1 comprises the sequence set forth in SEQ ID NO: 12 or 42,
e. the CDR-L2 comprises the sequence set forth in SEQ ID NO: 13 or 43, and
f. the CDR-L3 comprises the sequence set forth in SEQ ID NO: 14 or 44.
2 . The method of claim 1 , wherein the antibody comprises:
a. the CDR-H1 comprises the sequence set forth in SEQ ID NO: 39,
b. the CDR-H2 comprises the sequence set forth in SEQ ID NO: 40,
c. the CDR-H3 comprises the sequence set forth in SEQ ID NO: 41,
d. the CDR-L1 comprises the sequence set forth in SEQ ID NO: 42,
e. the CDR-L2 comprises the sequence set forth in SEQ ID NO: 43, and
f. the CDR-L3 comprises the sequence set forth in SEQ ID NO: 44.
3 . The method of claim 1 , wherein the antibody comprises the VH sequence shown in SEQ ID NO: 1, 3, or 5.
4 . The method of claim 1 , wherein the antibody comprises the VH sequence shown in SEQ ID NO: 1, 3, or 5 and the VL sequence shown in SEQ ID NO: 2, 4, or 6.
5 . The method of claim 1 , wherein the antibody comprises the VH sequence shown in SEQ ID NO: 1.
6 . The method of claim 1 , wherein the antibody comprises the VL sequence shown in SEQ ID NO: 2.
7 . The method of claim 1 , wherein the antibody comprises the VH sequence shown in SEQ ID NO: 1 and the VL sequence shown in SEQ ID NO: 2.
8 . The method of claim 1 , wherein the antibody comprises the heavy chain sequence shown in SEQ ID NO: 25 and the light chain sequence shown in SEQ ID NO: 26.
9 . The method of claim 1 , wherein the antibody binds to human TREM2 with a KD of less than or equal to 5.12×10-9 M, as measured by surface plasmon resonance (SPR) assay.
10 . The method of claim 1 , wherein the antibody is capable of specifically killing, depleting, or disabling TREM2+ myeloid cells.
11 . The method of claim 1 , wherein the antibody has antibody-dependent cell-mediated cytotoxicity (ADCC) activity, antibody-mediated cellular phagocytosis (ADCP) activity or complement-dependent cytotoxicity (CDC) activity.
12 . The method of claim 1 , wherein the antibody is a monoclonal antibody.
13 . The method of claim 1 , wherein the antibody is afucosylated.
14 . The method of claim 1 , wherein the antibody comprises a heavy chain constant region of human IgG1.
15 . The method of claim 1 , wherein the subject has previously received, is concurrently receiving, or will subsequently receive an immunotherapy.
16 . The method of claim 15 , wherein the immunotherapy is at least one of: a checkpoint inhibitor; a checkpoint inhibitor of T cells; anti-PD1 antibody; anti-PDL1 antibody; anti-CTLA4 antibody; adoptive T cell therapy; CAR-T cell therapy; a dendritic cell vaccine; a monocyte vaccine; an antigen binding protein that binds both a T cell and an antigen presenting cell; a BiTE dual antigen binding protein; a toll-like receptor ligand; a cytokine; a cytotoxic therapy; a chemotherapy; a radiotherapy; a small molecule inhibitor; a small molecule agonist; an immunomodulator; and an epigenetic modulator.
17 . The method of claim 16 , wherein the immunotherapy is selected from the group consisting of: an anti-PD1 antibody, an anti-PDL1 antibody; or an anti-CTLA4 antibody.