Use of lactoferrin for generating myeloid-derived suppressor cells
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Publication Number
US-12295990-B2
Publication Date
2025-05-13
Expiration Date
Abstract
Provided herein are methods of generating MDSCs ex vivo. The methods include culturing blood cells with lactoferrin.
Core Innovation
The invention relates to generating Myeloid-derived suppressor cells (MDSCs) by using lactoferrin (LF). Blood cells are cultured with lactoferrin in order to generate and/or expand MDSCs ex vivo, using umbilical cord blood cells or blood cells from a newborn subject.
The described concept further addresses that the generated MDSCs are characterized and functionally defined in terms of suppressive activity. The LF-driven accumulation includes suppressive PMN-MDSC and M-MDSC in newborn contexts, and includes phenotype markers and T-cell suppression. The LF dependence is supported by lactoferrin knockout models and by outcomes that change with MDSC depletion or transfer.
The therapeutic use is described for inflammatory diseases, with emphasis on pediatric/neonatal conditions. Necrotizing enterocolitis (NEC) is specifically highlighted, including that NEC outcomes worsen or improve depending on MDSC depletion or transfer. The document also indicates an in vitro assessment framework for human LF-treated MDSCs.
Claims Coverage
The provided independent claim set includes one independent claim covering an ex vivo culture method that uses lactoferrin to generate MDSCs from newborn-associated blood sources, with a defined lactoferrin-culture duration window. Dependent claims refine the method by specifying lactoferrin-related conditions, including optional culture-medium components, MDSC phenotype characterizations, and functional T-cell suppressive activity, and further include downstream composition/administration parameters for treating or preventing inflammatory disease.
Ex vivo culture of newborn blood cells with lactoferrin to generate MDSCs
A method of generating Myeloid-derived suppressor cells (MDSCs) ex vivo by culturing blood cells with lactoferrin for about 1 hour to about 48 hours, wherein said blood are umbilical cord blood cells or blood cells from a newborn subject.
Ex vivo culture with a specified lactoferrin concentration range
The method further includes lactoferrin present at 0.3–1.0 mg/ml.
Ex vivo culture medium further including IL-6
The method further includes that the culture medium further includes IL-6.
MDSC phenotype defined by CD marker expression patterns
The method further specifies that the MDSCs exhibit one of several defined phenotypes characterized by particular CD marker expression patterns.
MDSCs with T cell suppressive activity
The method further includes that the MDSCs exhibit T cell suppressive activity.
Pharmaceutical composition cell-count range for treatment or prevention
The composition comprises between 1×10^5 and 1×10^14 cells.
Overall, the claim coverage centers on an ex vivo lactoferrin-driven method for generating MDSCs from umbilical cord blood or newborn blood within a defined time window, with further refinements for lactoferrin concentration, optional IL-6 in the culture medium, MDSC phenotype characterization, and functional T-cell suppressive activity. Additional dependent subject matter includes a defined cell-count range for a composition used to treat or prevent inflammatory disease.
Stated Advantages
Enables generating or expanding suppressive PMN-MDSC and M-MDSC populations using lactoferrin.
Provides MDSCs with T cell suppressive activity as a functional property.
Supports therapeutic modulation of inflammatory disease outcomes, including necrotizing enterocolitis (NEC), with improvement or worsening depending on MDSC depletion or transfer.
Documented Applications
Treating or preventing inflammatory disease, with emphasis on pediatric/neonatal conditions.
Necrotizing enterocolitis (NEC), including outcomes associated with MDSC depletion or transfer.
Bronchopulmonary dysplasia (BPD) and sepsis are mentioned among the inflammatory disease contexts in the partial content.
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