Monocyte modulation and control of tumor metastasis
Inventors
Hedrick, Catherine C. • Hanna, Richard
Assignees
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Publication Number
US-11053297-B2
Publication Date
2021-07-06
Expiration Date
Abstract
Disclosed herein are methods of increasing numbers of monocytes to a tumor or cancer metastasis site in a subject. Non-limiting embodiments include administering or using a Nur77 polypeptide or subsequence thereof; a Nur77 agonist; a CX3CR1 agonist; CD14+ CD16+ monocytes and/or CD14dimCD16+ (CD115+CD11b+ GR1− (Ly6C−)) monocytes; CD14+ CD16+ monocytes and/or CD14dimCD16+ (CD115+CD11b+GR1− (Ly6C−)) monocytes contacted with a Nur77 agonist or contacted with a CX3CR1 agonist. Also disclosed herein are methods of increasing, stimulating, activating or promoting monocyte migration to or mobilization against a tumor or cancer metastasis in a subject. Non-limiting embodiments include administering a Nur77 polypeptide or subsequence thereof; a Nur77 agonist; a CX3CR1 agonist; CD14+ CD16+ monocytes and/or CD14dimCD16+ (CD115+CD11b+GR1− (Ly6C−)) monocytes; or CD14+ CD16+ monocytes and/or CD14dimCD16+ (CD115+CD11b+GR1− (Ly6C−)) monocytes contacted with a Nur77 agonist or contacted with a CX3CR1 agonist.
Core Innovation
The invention provides methods of controlling, limiting, or decreasing metastasis of a tumor or cancer in a subject by administering CD14+CD16+ monocytes and/or CD14dimCD16+ (CD115+CD11b+GR1− (Ly6C−)) monocytes. The method is directed to a subject having or at risk of having a cancer or tumor, and the metastasis of the tumor or cancer in the subject is controlled, limited or decreased.
The disclosed concept further relates to directing monocyte subsets to tumor/cancer metastasis sites and enabling them to patrol, migrate, and/or extravasate. The patent text links monocyte activity at metastasis sites to removing tumor material in a CX3CR1-dependent manner, thereby controlling or limiting metastasis, with particular relevance to initial lung metastasis.
Mechanistic rationale is provided through the biology of Nur77 (NR4A1/TR3/NGFIB) and CX3CR1 in cancer and monocytes. The disclosed approach includes modulation of Nur77 and/or CX3CR1 in connection with patrolling monocytes, and it is supported by referenced experimental observations described in the document.
Claims Coverage
The document includes one independent claim covering a metastasis-controlling method with one inventive feature centered on administering defined monocyte subsets to a subject to control, limit, or decrease metastasis; dependent claims further refine the cancer/tumor scope, metastatic effect, anatomical site, and monocyte biology.
Administering CD14+CD16+ and/or CD14dimCD16+ monocytes to control metastasis
A method of controlling, limiting, or decreasing metastasis of a tumor or cancer in a subject, comprising administering CD14+CD16+ monocytes and/or CD14dimCD16+ (CD115+CD11b+GR1− (Ly6C−)) monocytes to a subject having or at risk of having a cancer or tumor, wherein the metastasis of the tumor or cancer in the subject is controlled, limited or decreased.
Across the independent-claim scope, the core inventive concept is administering CD14+CD16+ and/or CD14dimCD16+ (CD115+CD11b+GR1− (Ly6C−)) monocytes to control, limit, or decrease metastasis of a tumor or cancer; dependent claims narrow the covered cancers, metastasis outcome characteristics, optionally specify lung metastasis, and further define monocyte-related effects.
Stated Advantages
Controls, limits, or decreases metastasis of a tumor or cancer in a subject.
Limits or decreases metastasis at sites other than the original site.
Reduces, inhibits, suppresses, limits or controls growth or proliferation of a tumor or cancer metastasis at one or more sites other than the original site.
Can specifically target tumor or cancer metastasis in the lung.
Stimulates, promotes, increases or induces production, development, survival, proliferation, differentiation or activity of CD14+CD16+ or CD14dimCD16+ monocytes.
Documented Applications
Used to control, limit, or decrease tumor/cancer metastasis, including initial lung metastasis and metastasis at sites other than the original site.
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