Antibodies Against ILT2 and Use Thereof

A monoclonal antibody or antigen-binding fragment

• that binds a human leukocyte immunoglobulin-like receptor subfamily B member 1 (ILT2) epitope within a sequence of human ILT2 selected from VKKGQFPIPSITWEH (SEQ ID NO:
• 41), LELVVTGAYIKPTLS (SEQ ID NO:
• 42), VILQCDSQVAFDGFS (SEQ ID NO:
• 43) and WYRCYAYDSNSPYEW (SEQ ID NO:
• 44), or
• that binds ILT2 and inhibits direct interaction between said ILT2 and beta-2-microglobulin (B2M).

A method for producing an agent, the method comprising:

• A. a) obtaining an agent that binds to an ILT2 extracellular domain or fragment thereof,
• testing an ability of said agent to induce at least two of:
• increased phagocytosis of a cancer cell by macrophages, increased T cell activity against a cancer cell, increased generation of M1 macrophages, reduced generation of M2 macrophages, increased recruitment of dendritic cells to a tumor microenvironment, increased dendritic cell activation and increased natural killer (NK) cell cytotoxicity against a cancer cell and
• selecting at least one agent that induces at least two of said increased phagocytosis, said increased activity, said increased generation, said reduced generation, said recruitment, said increased activation, said decreased activity and said increased cytotoxicity;
• or
• b) culturing a host cell comprising one or more vectors comprising a nucleic acid sequence encoding an agent, wherein the nucleic acid sequence is that of an agent that was selected by:
• i. obtaining an agent that binds to an ILT2 extracellular domain or fragment thereof;
• ii. testing an ability of said agent to induce at least two of:
• increased phagocytosis of a cancer cell by macrophages, increased T cell activity against a cancer cell, increased generation of M1 macrophages, reduced generation of M2 macrophages, increased recruitment of dendritic cells to a tumor microenvironment, increased dendritic cell activation and increased natural killer (NK) cell cytotoxicity against a cancer cell;
• and
• iii. selecting at least one agent that increases at least two of said increased phagocytosis, said increased activity, said increased generation, said reduced generation, said recruitment, said increased activation, said decreased activity and said increased cytotoxicity;
• thereby producing an agent, or
• B. a) obtaining an agent that binds to an ILT2 extracellular domain or fragment thereof,
• testing an ability of said agent to increase efficacy of an anti-PD-L1/PD-1 based therapy against a cancer cell and selecting at least one agent that increases the efficacy of an anti-PD-L1/PD-1 based therapy;
• or
• b) culturing a host cell comprising one or more vectors comprising a nucleic acid sequence encoding an agent, wherein the nucleic acid sequence is that of an agent that was selected by:
• i. obtaining an agent that binds to an ILT2 extracellular domain or fragment thereof;
• ii. testing an ability of said agent to increase efficacy of an anti-PD-L1/PD-1 based therapy against a cancer cell;
• and
• iii. selecting at least one agent that increases efficacy of an anti-PD-L1/PD-1 based therapy against a cancer cell;
• thereby producing an agent.

A method for producing an agent, the method comprising:

• A. obtaining an agent that binds to an ILT2 extracellular domain or fragment thereof,
• testing an ability of said agent to inhibit interaction between ILT2 and B2M and
• selecting at least one agent that inhibits interaction between ILT2 and B2M;
• or
• b) culturing a host cell comprising one or more vectors comprising a nucleic acid sequence encoding an agent, wherein the nucleic acid sequence is that of an agent that was selected by:
• i. obtaining an agent that binds to an ILT2 extracellular domain or fragment thereof;
• ii. testing an ability of said agent to inhibit interaction between ILT2 and B2M;
• and
• iii. selecting at least one agent that inhibits interaction between ILT2 and B2M;
• thereby producing an agent, or
• B. a) obtaining an agent that binds to an ILT2 epitope within a sequence of human ILT2 selected from SEQ ID NO:
• 41, 42, 43 and 44, or
• b) culturing a host cell comprising one or more vectors comprising a nucleic acid sequence encoding an agent, wherein the nucleic acid sequence is that of an agent that was selected by obtaining an agent that binds to an ILT2 epitope within a sequence of human ILT2 selected from SEQ ID NO:
• 41, 42, 43 and 44;
• thereby producing an agent.