Modulation of stimulatory and non-stimulatory myeloid cells
Provided herein 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, comprising killing, disabling, or depleting non-stimulatory myeloid cells using an antigen binding protein such as an antibody or antigen binding fragment thereof.
1. A method of treating a cancer in a subject, comprising:
a. determining the presence of Triggering Receptor Expressed on Myeloid Cells 2 positive (TREM2+) myeloid cells from a cancer sample obtained from the subject; and
b. administering to the subject an antibody or antigen-binding fragment thereof comprising a human Fc domain, wherein the antibody or antigen-binding fragment thereof binds to the extracellular domain TREM2, wherein the antibody or antigen-binding fragment thereof is present in an amount effective to kill, disable, or deplete the TREM2+ myeloid cells via antibody-dependent cell-mediated cytotoxicity activity, antibody-dependent phagocytosis activity, complement-dependent cytotoxicity activity, or antibody-mediated phagocytosis activity.
2. The method of claim 1 , wherein the cancer sample is obtained by needle biopsy, punch biopsy, or surgical excision.
3. The method of claim 1 , wherein the determining step comprises determining the presence of TREM2 mRNA expression or TREM2 protein expression.
4. The method of claim 1 , wherein the determining step is carried out using at least one of polymerase chain reaction (PCR), quantitative PCR (qPCR), RT-qPCR, microarray, gene array, RNAseq, and a cell sorting method.
5. The method of claim 4 , wherein the cell sorting method comprises at least one of fluorescence activated cell sorting, flow-cytometry, magnetic-activated cell sorting, microraft sorting, and affinity-based cell separation.
6. The method of claim 1 , wherein the antibody is at least one of a monoclonal antibody, an IgG1 antibody, an IgG4 antibody, an afucosylated antibody, a human antibody, a humanized antibody, a chimeric antibody, and a full length antibody.
7. The method of claim 6 , wherein the human Fc is a human IgG1 Fc.
8. The method of claim 6 , wherein the antibody is an afucosylated antibody.
9. The method of claim 6 , wherein the antibody is a humanized antibody.
10. The method of claim 1 , wherein the administering induces at least one of death of the TREM2+ myeloid cells, apoptosis of the TREM2+ myeloid cells, lysis of the TREM2+ myeloid cells, phagocytosis of the TREM2+ myeloid cells, and growth arrest in the TREM2+ myeloid cells.
11. The method of claim 1 , wherein the cancer is a solid cancer or a liquid cancer.
12. The method of claim 11 , wherein the cancer is selected from the group consisting of: melanoma, kidney, hepatobiliary, head-neck squamous carcinoma, pancreatic, colon, bladder, glioblastoma, prostate, lung, and breast.
13. The method of claim 1 , wherein the subject has previously received an immunotherapy.
14. The method of claim 13 , wherein the immunotherapy comprises at least one of pembrolizumab, nivolumab, and ipilimumab.
15. The method of claim 1 , further comprising administering an immunotherapy to the subject concurrently with the antibody or antigen-binding fragment thereof, wherein the immunotherapy comprises at least one of pembrolizumab, nivolumab, or ipilimumab.
16. The method of claim 1 , further comprising administering an immunotherapy to the subject subsequently to the antibody or antigen-binding fragment thereof, wherein the immunotherapy comprises at least one of pembrolizumab, nivolumab, or ipilimumab.
17. A method of killing, disabling, or depleting TREM2+ myeloid cells comprising:
a. determining the presence of TREM2+ myeloid cells from a cancer sample obtained from a subject with cancer; and
b. contacting the TREM2+ myeloid cells present in the cancer of the subject with an antibody or antigen-binding fragment thereof comprising a human Fc domain, wherein the antibody or antigen-binding fragment thereof binds to the extracellular domain of TREM2; wherein the antibody or antigen-binding fragment thereof is present in an amount effective to kill, disable, or deplete the TREM2+ myeloid cells via antibody-dependent cell-mediated cytotoxicity activity, antibody-dependent phagocytosis activity, complement-dependent cytotoxicity activity, or antibody-mediated phagocytosis activity.
18. The method of claim 17 , wherein the antibody is at least one of a humanized antibody, an IgG1 antibody, or an afucosylated antibody.
19. The method of claim 17 , wherein the contacting induces at least one of death of the TREM2+ myeloid cells, apoptosis of the TREM2+ myeloid cells, lysis of the TREM2+ myeloid cells, phagocytosis of the TREM2+ myeloid cells, and growth arrest in the TREM2+ myeloid cells.
20. The method of claim 17 , wherein the cancer is a solid cancer or a liquid cancer.
21. The method of claim 20 , wherein the cancer is selected from the group consisting of: melanoma, kidney, hepatobiliary, head-neck squamous carcinoma, pancreatic, colon, bladder, glioblastoma, prostate, lung, and breast.