Motile sperm domain containing protein 2 and cancer
Inventors
Mendel, Itzhak • Propheta-Meiran, Oshrat • Salem, Yaniv • SHOHAM, Anat • Yacov, Niva • Breitbart, Eyal
Assignees
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Publication Number
US-11945875-B2
Publication Date
2024-04-02
Expiration Date
Abstract
Disclosed herein are methods of treating, reducing the incidence of, or preventing one or more activities in or of a cancer cell, methods of treating, reducing the incidence of, or preventing migration or metastasis of a cancer cell, methods of treating, reducing the incidence of, or preventing a cancer by reducing tumor associated macrophages (TAMs) or their migration, and methods of treating, reducing the incidence of, or preventing a cancer (including metastatic cancer), for example, with an inhibitor of Motile Sperm Domain containing Protein 2 (MOSPD2). Also disclosed are inhibitors of MOSPD2 (e.g., anti-MOSPD2 antibodies or antigen binding fragments thereof) and pharmaceutical compositions containing MOSPD2 inhibitors. Also disclosed are methods for the prediction, diagnosis, or prognosis of cancer, cancer metastasis, tumor progression, or tumor invasiveness in a subject.
Core Innovation
MOSPD2 is described as a conserved 518-aa protein implicated in chemokine-directed migration and metastasis. The document connects MOSPD2 to cancer cell migration and to the migration of monocytes and tumor associated macrophages (TAMs), and describes MOSPD2 expression in cancer tissues with an association with invasive or metastatic progression.
The document frames the problem as treating, preventing, or reducing cancer, metastasis, and TAM presence or migration by targeting MOSPD2. It describes therapeutic approaches using administration of MOSPD2 inhibitors, including DNA or RNA inhibitors, DNA/RNA silencing agents such as RNA interference (siRNA, shRNA, miRNA) and CRISPR-Cas9, as well as anti-MOSPD2 antibodies or antigen-binding fragments including F(ab')2.
The document additionally relates diagnostic/prognostic prediction methods that use MOSPD2. It also provides chemistry and targeting rationales focused on oxidized phospholipid MOSPD2 inhibitors, including VB-201 and VB-221, with structural formulas and figure-captioned findings describing MOSPD2 silencing reducing migration and metastasis and antibody binding inhibiting migration and phosphorylation-related effects.
Claims Coverage
The provided content identifies one independent claim and dependent refinements. The independent claim covers treating cancer or cancer metastasis by administering a MOSPD2 inhibitor, with the cancer comprising MOSPD2-expressing cells, and the inhibitor being a DNA or RNA inhibitor.
Administer a MOSPD2 DNA or RNA inhibitor to treat cancer or metastasis
A method of treating cancer or metastasis of cancer in a subject by administering an inhibitor of MOSPD2.
DNA or RNA inhibitor for MOSPD2 targeting in MOSPD2-expressing cancer
The inhibitor is a DNA or RNA inhibitor, and the cancer comprises cells that express MOSPD2.
The inventive focus is administering a MOSPD2 inhibitor, specifically a DNA or RNA inhibitor, to treat cancer or metastasis where the cancer contains MOSPD2-expressing cells. Dependent refinements further reference nucleic-acid and RNA-interference formats and reduction of monocyte or TAM migration near or within the cancer mass.
Stated Advantages
Treating cancer or cancer metastasis in a subject by targeting MOSPD2.
Inhibiting migration and metastasis associated with MOSPD2-related cell migration.
Reducing monocytes or tumor-associated macrophages near or within a cancer mass in dependent formulations.
Reducing migration of circulating monocytes or tumor-associated macrophages near or within a mass of the cancer in dependent formulations.
Documented Applications
Treating cancer in a subject, including cancer types described in dependent claim refinements such as glioblastoma and malignant ascites.
Treating cancer metastasis in a subject where the cancer comprises cells that express MOSPD2.
Diagnostic/prognostic prediction methods using MOSPD2.
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