Treating cancer by blocking the interaction of TIM-3 and its ligand
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Publication Number
US-12227567-B2
Publication Date
2025-02-18
Expiration Date
Abstract
Provided herein are methods of activating immune response and/or treating cancer in a patient comprising administering to the patient a Gal3:TIM-3 inhibitor that interferes with the interaction between Gal3 and TIM-3, where said inhibitor is administered in an amount sufficient to activate immune response. Also provided are a humanized anti-Gal3 antibodies that can block the interaction between Gal3 and TIM3 and methods of using the anti-Gal3 antibody to treat cancer. Methods for determining if a patient's cancer is suitable for treatment with a Gal3:TIM-3 inhibitor and methods for selecting compounds that can block interaction between Gal3 and TIM-3, activating immune response and/or treating cancer are also provided.
Core Innovation
The invention relates to anti-cancer immunotherapy by blocking Galectin-3 (Gal3) interaction with TIM-3. TIM-3 specifically binds Gal3, leading to suppressed T-cell activation, and interfering with the Gal3-TIM-3 interaction restores and activates immune responses.
The anti-Gal3 immunotherapy includes Gal3:TIM-3 inhibitors, including humanized anti-Gal3 antibodies, to interfere with the Gal3-TIM-3 interaction. Gal3 is overexpressed on cells in the tumor microenvironment and TIM-3 is expressed on immune cells, and immune activation reduces tumor burden.
Patient selection is described by measuring Gal3 surface levels on primary cancer or tumor microenvironment cells and comparing to threshold activity values. The antibody concept defines light chain variable region complementary determining regions CDR L1, CDR L2, and CDR L3 and heavy chain variable region complementary determining regions CDR H1, CDR H2, and CDR H3 using specified SEQ ID NOs, and the anti-Gal3 antibodies can be humanized or human antibodies.
Claims Coverage
The partial content contains three independent claims that cover activating an immune response in a cancer patient by administering anti-Gal3 antibodies that interfere with the interaction between Gal3 and TIM-3, with specific variable-region and CDR sequence definitions.
Activating an immune response by interfering with Gal3-TIM-3 interaction
A method of activating an immune response in a patient with a cancer, comprising administering to the patient an effective amount of an anti-Gal3 antibody that interferes with the interaction between Gal3 and TIM-3.
CDR-defined light and heavy chain variable regions for anti-Gal3 antibodies
The anti-Gal3 antibody comprises a light chain variable region including CDR L1, CDR L2, and CDR L3 and a heavy chain variable region including CDR H1, CDR H2, and CDR H3, wherein CDR L1 comprises the amino acid sequence of SEQ ID NO:17, CDR L2 comprises the amino acid sequence of SEQ ID NO:18, CDR L3 comprises the amino acid sequence of SEQ ID NO:19, CDR H1 comprises the amino acid sequence of SEQ ID NO:9, CDR H2 comprises the amino acid of SEQ ID NO:10, and CDR H3 comprises the amino acid sequence of SEQ ID NO:11.
Humanized anti-Gal3 antibody format
The anti-Gal3 antibody is a humanized antibody or a human antibody, including a humanized antibody in the method of claim 10.
Means for inhibiting Gal3-TIM-3 interaction as CDR-defined antibody variable regions
A method of activating immune response in a patient by administering an antibody wherein the antibody includes a means for inhibiting the interaction between Gal3 and TIM-3, and wherein the means for inhibiting the interaction comprises a light chain variable region with CDR L1, CDR L2, and CDR L3 and a heavy chain variable region with CDR H1, CDR H2, and CDR H3 defined by the specified SEQ ID NO:17, SEQ ID NO:18, SEQ ID NO:19, SEQ ID NO:9, SEQ ID NO:10, and SEQ ID NO:11 sequences.
Across the independent claims, the core claim coverage is the use of anti-Gal3 antibodies, defined by specific CDR sequences in light and heavy chain variable regions, administered in an amount sufficient to activate an immune response by interfering with the Gal3-TIM-3 interaction in the patient, with embodiments specifying humanized or human antibody format.
Stated Advantages
Activating an immune response in a cancer patient by interfering with the Gal3-TIM-3 interaction.
Reducing cancer burden by activating immune responses in the tumor microenvironment.
Documented Applications
Anti-cancer immunotherapy involving activation of immune responses in patients with cancer where Gal3 is overexpressed in the tumor microenvironment and TIM-3 is expressed on immune cells.
Immune response activation methods with patient-selection based on measuring Gal3 surface levels and comparing to threshold activity values.
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