Antibodies against ILT2 and use thereof
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-12071479-B2
Publication Date
2024-08-27
Expiration Date
Abstract
The present disclosure provides monoclonal anti-ILT2 antibodies or antigen-binding fragments thereof, as well as pharmaceutical compositions comprising the same and methods of producing the same. Also provided are methods of treating cancer using the antibodies or compositions of the present disclosure. Methods of patient selection are also provided.
Core Innovation
The invention relates to monoclonal anti-immunoglobulin-like transcript 2 (ILT2) antibodies, including ILT2A IgG4 antibodies, comprising defined CDR-H1-3 and CDR-L1-3 regions characterized by specified SEQ ID NOs. The antibodies comprise a human IgG4 heavy chain constant region comprising an S228P mutation, an L235E mutation, or both (Eu numbering), defining a particular ILT2-binding antibody format intended to interfere with ILT2-mediated immune regulation.
The invention emphasizes ILT2 inhibition by binding ILT2 extracellularly and blocking ILT2–B2M interaction, including functional blockade of ILT2 interactions involving HLA-G/ILT2 and ILT2–B2M. By inhibiting these ILT2 interactions, the patent describes downstream immune activation effects, including enhanced macrophage phagocytosis, NK cytotoxicity, and T cell activity.
The disclosed approach further includes therapeutic co-administration and combination with PD-1/PD-L1 therapies. The patent describes synergy or additive effects with PD-1/PD-L1 therapy in connection with ILT2 blockade, and it also describes formulation and kit aspects, along with production and identification selection based on ILT2 binding and ILT2–B2M inhibition readouts.
Claims Coverage
The independent claim set covers three inventive features centered on monoclonal ILT2/ILT2A IgG4 antibodies defined by specific CDR sequence identifiers and human IgG4 constant-region S228P and/or L235E mutations. The independent claim set also supports therapeutic use directed to HLA-G or MHC-I expressing cancers and includes adjunct/combination contexts with anti-PD-L1 or anti-PD-1 immunotherapy.
Sequence-defined ILT2A IgG4 antibody with human IgG4 constant-region mutations
A monoclonal anti-immunoglobulin-like transcript 2 (ILT2A) IgG4 antibody comprising three heavy chain CDRs (CDR-H1-3) and three light chain CDRs (CDR-L1-3) wherein the CDR-H1-3 and CDR-L1-3 comprise specified SEQ ID NOs, and wherein the antibody comprises a human IgG4 heavy chain constant region comprising an S228P mutation, an L235E mutation, or both (Eu numbering).
Monoclonal antibody defined by heavy and light chains SEQ ID NOs 48 and 49
A monoclonal antibody comprising a heavy chain and a light chain, wherein the heavy and light chains comprise SEQ ID NOs 48 and 49, respectively.
Sequence-defined anti-ILT2 antibody with specified CDR SEQ ID NOs and human IgG4 constant-region mutations
A monoclonal anti-immunoglobulin-like transcript 2 (ILT2) antibody comprising CDR-H1-3 and CDR-L1-3 that comprise specified SEQ ID NOs, wherein the antibody comprises a human IgG4 heavy chain constant region comprising an S228P mutation, an L235E mutation, or both (Eu numbering).
Across the independent claims, the patent’s claimed scope centers on monoclonal ILT2/ILT2A IgG4 antibodies defined by specific CDR sequence identifiers and human IgG4 constant-region S228P and/or L235E mutations. The independent claim set also supports therapeutic use directed to HLA-G or MHC-I expressing cancers and includes adjunct/combination contexts with anti-PD-L1 or anti-PD-1 immunotherapy.
Stated Advantages
Inhibit ILT2-mediated immune suppression, including the ILT2–B2M interaction.
Treat HLA-G or MHC-I expressing cancers.
Increase the effectiveness of an anti-PD-L1 or anti-PD-1 therapy against cancer cells expressing HLA-G or MHC-I.
Synergistic or additive enhancement of PD-1/PD-L1 therapy effects when combined with ILT2 blockade.
Immune activation effects including enhanced macrophage phagocytosis, NK cytotoxicity, and T cell activity.
In vivo xenograft/metastasis efficacy observations associated with the ILT2 inhibition approach.
Documented Applications
Treating an HLA-G or MHC-I expressing cancer in a human patient by administering the monoclonal anti-ILT2 or anti-ILT2A antibody.
Increasing the effectiveness of an anti-PD-L1-based therapy or anti-PD-1-based therapy against cancer cells expressing HLA-G or MHC-I by administering the monoclonal anti-ILT2 or anti-ILT2A antibody.
Adjunct or combination therapy context that includes an opsonizing agent example including an EGFR inhibitor, cetuximab.
Pharmaceutical composition use of the claimed antibodies with a pharmaceutically acceptable excipient.
Interested in licensing this patent?