Methods of use for anti-ILT2 antibodies
Inventors
Mandel, Ilana • PERETZ, Tsuri • HAVES ZIV, Dana • GOLDSHTEIN, Ilana • ALISHEKEVITZ, DROR • FRIDMAN-DROR, Anna • HAKIM, MOTTI • Shulman, Avidor • Sapir, Yair • Ben-Moshe, Tehila
Assignees
Interested in licensing this patent?
MTEC can help explore whether this patent might be available for licensing for your application.
Publication Number
US-12391755-B2
Publication Date
2025-08-19
Expiration Date
Abstract
The present invention provides monoclonal antibodies, or antigen-binding portions thereof, against ILT2, as well as pharmaceutical compositions comprising same and methods of producing same. Also provided are methods of treating cancer comprising administering the antibodies or compositions of the invention. Methods of treating cancer, combination treatments, and patient selection are also provided.
Core Innovation
ILT2 (LILRB1/CD85j) functions as an immune-suppressive checkpoint on immune cells and tumor cells, and ILT2 is linked to HLA-G1 expression. In the disclosed cancer context, ILT2 linkage and/or HLA-G1 expression are associated with poor cancer outcomes. The patent discloses antagonizing ILT2 rather than agonizing it.
The invention provides an anti-ILT2 monoclonal antibody or antigen-binding fragment. The antibody comprises three heavy chain CDRs and three light chain CDRs, with HCDR1-3 and LCDR1-3 comprising specified SEQ ID NO-defined CDR sets. A defined position X in SEQ ID NO:15 is selected from A, C, and S, and alternative permitted CDR sets are provided.
The disclosed anti-ILT2 antibodies bind an ILT2 interdomain epitope between D1 and D2 and antagonize ILT2 interactions, including the ILT2-B2M interaction, without agonism. ILT2 blockade is reported to increase anti-tumor immune functions including T-cell activation, proliferation, and cytotoxicity, NK cytotoxicity, macrophage phagocytosis and M1 inflammatory macrophage generation, and dendritic-cell activation and homing, while decreasing M2 suppressor macrophage generation.
The disclosure further relates ILT2 antagonism to improved efficacy when combined with anti-PD-1/PD-L1 therapy. It also describes treating cancers expressing HLA-G, MHC-I, or both, and patient selection based on ILT2/soluble HLA-G expression levels.
Claims Coverage
Independent claims are directed to methods that administer an anti-ILT2 monoclonal antibody or antigen-binding fragment with specified CDR composition and sequence variability. The main inventive features are anti-ILT2 antibody CDR-defined heavy/light chain sequence sets with an X-position constraint, treatment of HLA-G expressing cancer and/or MHC-I expressing cancer, and increasing efficacy of anti-PD-L1 or anti-PD-1 therapy against cancer cells expressing HLA-G and/or MHC-I.
Administration of an anti-ILT2 antibody with defined CDR sets and X constraint
A method comprising administering to the subject a monoclonal anti-immunoglobulin-like transcript 2 (ILT2) antibody or an antigen-binding fragment thereof, wherein the anti-ILT2 antibody comprises three heavy chain CDRs and three light chain CDRs, and wherein HCDR1-3 and LCDR1-3 comprise SEQ ID NO-defined CDRs where X in SEQ ID NO: 15 is selected from A, C, and S.
Inducing or enhancing anti-tumor immunity for treating HLA-G expressing or MHC-I expressing cancer
A method of inducing or enhancing an anti-tumor T-cell response, including increasing T-cell proliferation, reducing cancer-induced suppressor myeloid activity, increasing natural killer cell cytotoxicity, increasing macrophage phagocytosis, increasing generation of M1 inflammatory macrophages, decreasing generation of M2 suppressor macrophages, and increasing dendritic cell number and activation, comprising administering the specified anti-ILT2 antibody or antigen-binding fragment for treating an HLA-G expressing cancer or an MHC-I expressing cancer in a human subject.
Increasing efficacy of anti-PD-L1/PD-1 therapy for cancer cells expressing HLA-G and/or MHC-I
A method for treating cancer by increasing efficacy of an anti-PD-L1-based therapy or anti-PD-1-based therapy against a cancer cell expressing HLA-G, MHC-I, or both, comprising administering the specified anti-ILT2 monoclonal antibody or antigen-binding fragment.
The independent claims focus on administering an anti-ILT2 monoclonal antibody or antigen-binding fragment defined by specific HCDR and LCDR SEQ ID NO sets and an X position constraint. Claim scope covers treatment of HLA-G expressing cancer and/or MHC-I expressing cancer and, separately, increasing the efficacy of anti-PD-L1/PD-1 therapy against cancer cells expressing HLA-G and/or MHC-I.
Stated Advantages
Increases T-cell proliferation.
Reduces cancer-induced suppressor myeloid activity.
Increases natural killer cell cytotoxicity.
Increases macrophage phagocytosis.
Increases generation of M1 inflammatory macrophages.
Decreases generation of M2 suppressor macrophages.
Increases dendritic cell number in a tumor microenvironment.
Increases dendritic cell activation.
Improves efficacy of anti-PD-L1- or anti-PD-1-based therapy against cancer cells expressing HLA-G, MHC-I, or both.
Documented Applications
Treating an HLA-G expressing cancer in a human subject.
Treating an MHC-I expressing cancer in a human subject.
Treating cancer by increasing efficacy of anti-PD-L1- or anti-PD-1-based therapy against cancer cells expressing HLA-G, MHC-I, or both.
Interested in licensing this patent?