Anti-TREM2 antibodies and related methods
Inventors
Streuli, Michel • Sriram, Venkataraman • Pal, Aritra • Presta, Leonard G.
Assignees
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Publication Number
US-11505602-B2
Publication Date
2022-11-22
Expiration Date
Abstract
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, comprising killing, disabling, or depleting non-stimulatory myeloid cells using an anti-TREM2 antibody or antigen binding fragment thereof.
Core Innovation
The invention relates to treating cancer by determining the presence of Triggering Receptor Expressed on Myeloid Cells 2 positive (TREM2+) myeloid cells from a cancer sample obtained from a subject, and administering an isolated antibody that binds to human TREM2 (SEQ ID NO:15). The antibody is defined by specified heavy chain and light chain variable regions that each comprise three CDR sequences: CDR-H1, CDR-H2, and CDR-H3, and CDR-L1, CDR-L2, and CDR-L3. The CDR sequences are set forth by SEQ ID NO: 9, 10, 11, 12, 13, and 14.
The disclosed approach also includes killing, disabling, or depleting TREM2+ myeloid cells by determining the presence of TREM2+ myeloid cells from a cancer sample and administering the same isolated antibody that binds to human TREM2 (SEQ ID NO:15). The functional outcome is framed as killing, disabling, or depleting, and the antibody is further defined by the specified CDR composition using the stated SEQ ID NOs. Dependent claim refinements further require particular antibody attributes such as a human Fc region and Fc-mediated activities.
The invention associates targeting of TREM2+ myeloid cells with use alongside immunotherapy regimens. The dependent claims specify that the immunotherapy may be previously received, concurrently received, or subsequently received, and provide enumerated types of immunotherapy, including checkpoint inhibitor antibodies such as anti–PD-1, anti–PD-L1, and anti–CTLA4. Additional refinements specify that the TREM2+ myeloid cells may comprise dendritic cells, tumor-associated macrophages (TAMs), neutrophils, or monocytes, including cases where the cells are intratumoral.
Claims Coverage
The independent claims are directed to two methods: treating cancer and killing, disabling, or depleting TREM2+ myeloid cells. Both independent claims share the core inventive feature of determining TREM2+ myeloid cells from a cancer sample and administering an isolated human TREM2-binding antibody defined by specific CDR-H1/H2/H3 and CDR-L1/L2/L3 sequences (SEQ ID NOs: 9-14).
Treating cancer by determining TREM2+ myeloid cells and administering a CDR-defined anti-human TREM2 antibody
A method of treating cancer in a subject in need thereof, comprising determining the presence of TREM2+ myeloid cells from a cancer sample and administering an isolated antibody that binds to human TREM2 (SEQ ID NO:15), where the antibody has a heavy chain with VH comprising CDR-H1, CDR-H2, and CDR-H3 and a light chain with VL comprising CDR-L1, CDR-L2, and CDR-L3, with CDR-H1=SEQ ID NO:9, CDR-H2=SEQ ID NO:10, CDR-H3=SEQ ID NO:11, CDR-L1=SEQ ID NO:12, CDR-L2=SEQ ID NO:13, and CDR-L3=SEQ ID NO:14.
Killing, disabling, or depleting TREM2+ myeloid cells by determining TREM2+ myeloid cells and administering a CDR-defined anti-human TREM2 antibody
A method of killing, disabling, or depleting TREM2+ myeloid cells of a subject, comprising determining the presence of TREM2+ myeloid cells from a cancer sample and administering an isolated antibody that binds to human TREM2 (SEQ ID NO:15), where the antibody has a heavy chain with VH comprising CDR-H1, CDR-H2, and CDR-H3 and a light chain with VL comprising CDR-L1, CDR-L2, and CDR-L3, with CDR-H1=SEQ ID NO:9, CDR-H2=SEQ ID NO:10, CDR-H3=SEQ ID NO:11, CDR-L1=SEQ ID NO:12, CDR-L2=SEQ ID NO:13, and CDR-L3=SEQ ID NO:14.
Both independent claims cover a two-part approach: determine TREM2+ myeloid cells in a cancer sample and administer an isolated human TREM2-binding antibody defined by the specified heavy- and light-chain CDR sets (SEQ ID NOs: 9–14). Claim refinements in the provided claim set further constrain treatment context (immunotherapy), antibody composition (e.g., human Fc region), and antibody effector functions (ADCC/CDC/ADCP), and specify which TREM2+ myeloid cell types may be targeted.
Stated Advantages
Treating cancer by determining the presence of TREM2+ myeloid cells and administering an isolated antibody that binds to human TREM2.
Killing, disabling, or depleting TREM2+ myeloid cells.
Targeting additional antibody properties for functional constraints, including at least one of ADCC, CDC, and ADCP activities.
Documented Applications
Methods for treating cancer in a subject in need thereof by determining the presence of TREM2+ myeloid cells and administering an isolated human TREM2-binding antibody.
Methods for killing, disabling, or depleting TREM2+ myeloid cells in a subject based on determination of TREM2+ myeloid cells from a cancer sample.
Use of the method in combination with immunotherapy, including checkpoint inhibitor antibodies such as anti-PD1, anti-PD-L1, and anti-CTLA4, and other enumerated immunotherapy types.
Detection/quantification of TREM2/NSM cells and functional in vivo examples are referenced in the partial content via figures, including tumor control with PI-7012+anti-PD-1 and macrophage depletion localized to the TME, as described in the provided summary text.
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