Compositions including a therapeutic antibodies and/or a checkpoint inhibitor and an integrin activating compound
Inventors
Woodside, Darren G. • Vanderslice, Peter • Marathi, Upendra K.
Assignees
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Publication Number
US-12201686-B2
Publication Date
2025-01-21
Expiration Date
Abstract
Pharmaceutical compositions including one or more integrin activating compounds capable of enhancing an anti-tumor activity of one or more therapeutic antibodies, one or more immune checkpoint inhibitors, or mixtures thereof.
Core Innovation
The patent describes a pharmaceutical composition that combines one or more integrin activating compounds with one or more therapeutic antibodies and/or one or more immune checkpoint inhibitors, including mixtures of a therapeutic antibody and a checkpoint inhibitor. The integrin activating compounds are capable of enhancing the activity of the therapeutic antibodies, the immune checkpoint inhibitors, or the mixture.
The disclosed concept increases integrin-mediated adhesion by targeting integrins α4β1, α4β7, α5β1, αLβ2, and in some cases αvβ3, to their ligands VCAM-1, fibronectin, MAdCAM-1, ICAM-1/ICAM-2, and vitronectin. The increased adhesion is described as occurring through integrin activation that enhances Fc-mediated effector-target adhesion and potentiates antibody dependent cellular cytotoxicity (ADCC).
The patent describes small-molecule integrin ligand mimetics as integrin activating compounds and presents them as potentiators of anti-tumor activity and immunotherapy outcomes. The disclosed chemical scope is based on a general Formula (I), together with specific compound examples, and is discussed in combination contexts with therapeutic antibodies and immune checkpoint inhibitors, including therapeutically ineffective doses plus an integrin activator.
Claims Coverage
The document explicitly provides one independent claim. The claim coverage centers on a pharmaceutical composition combining integrin activating compounds with therapeutic antibodies and/or immune checkpoint inhibitors, where the integrin activating compounds enhance the activity of the antibody, the checkpoint inhibitor, or the mixture.
Integrin activators enhancing antibody and checkpoint inhibitor activity in a composition
A pharmaceutical composition comprising one or more integrin activating compounds and one or more therapeutic antibodies, one or more immune checkpoint inhibitors, or mixtures, wherein the one or more integrin activating compounds are capable of enhancing an activity of the one or more therapeutic antibodies, the one or more immune checkpoint inhibitors, or the mixture of the therapeutic antibody and the checkpoint inhibitor.
Across the independent claim, the key inventive theme is combining integrin activating compounds with therapeutic antibodies and/or immune checkpoint inhibitors in a single pharmaceutical composition, with the integrin activating compounds enhancing the activity of the antibody and/or checkpoint inhibitor regimen, including antibody–checkpoint inhibitor mixtures.
Stated Advantages
Enhances an activity of one or more therapeutic antibodies and/or one or more immune checkpoint inhibitors.
Potentiates antibody dependent cellular cytotoxicity (ADCC) via enhanced Fc-mediated effector-target adhesion.
Increases integrin-mediated adhesion through integrin activation to integrin ligands (VCAM-1, fibronectin, MAdCAM-1, ICAM-1/ICAM-2, and vitronectin).
Potentiates anti-tumor activity and improves immunotherapy outcomes.
Enhances vaccine priming, adoptive cell therapies, and ADCC when combined with Fc-containing therapeutic antibodies and/or immune checkpoint inhibitors.
Can be used with therapeutically ineffective doses of therapeutic antibodies and/or immune checkpoint inhibitors by adding an integrin activator to enhance activity.
In a melanoma model, increases median survival and supports long-term tumor-free rejection when a compound is added to GVAX®/anti-CTLA-4 (mAb clone 9H10).
Documented Applications
Cancer treatment regimens that include checkpoint blockade and chemotherapy and/or cancer vaccine, and adoptive cell therapy, using integrin enhancing compounds to increase integrin-mediated adhesion and ADCC.
A melanoma model regimen in which a compound such as C4 added to GVAX®/anti-CTLA-4 (mAb clone 9H10) increases median survival and supports long-term tumor-free rejection.
Used in immunotherapy contexts including cancer vaccines for vaccine priming.
Used with adoptive cell therapies, including NK cells, activated NK cells, engineered NK cells, NK-92, iNKT cells, γδT cells, CTLs, and chimeric antigen receptor cells.
Used in combination immunotherapy involving antibody-dependent cellular cytotoxicity (ADCC) together with Fc-containing therapeutic antibodies and/or immune checkpoint inhibitors, including regimens described as using therapeutically ineffective doses plus integrin activator.
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