Extracorporeal removal of microvesicular particles
Inventors
Ichim, Thomas • Tullis, Richard H.
Assignees
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Publication Number
US-8288172-B2
Publication Date
2012-10-16
Expiration Date
Abstract
The invention described herein teaches methods of removing microvesicular particles, which include but are not limited to exosomes, from the systemic circulation of a subject in need thereof with the goal of reversing antigen-specific and antigen-nonspecific immune suppression. Said microvesicular particles could be generated by host cells that have been reprogrammed by neoplastic tissue, or the neoplastic tissue itself. Compositions of matter, medical devices, and novel utilities of existing medical devices are disclosed.
Core Innovation
The invention relates to removing immune suppressive microvesicular particles from the blood of a subject in need thereof by establishing an extracorporeal circulation system. Whole blood, or components thereof, are contacted with a single or a plurality of agents capable of binding immune suppressive microvesicular particles found within the blood or the components, and the agents remove the immune suppressive microvesicular particles during extracorporeal contact.
After contacting, the method returns the contacted whole blood or components into the original blood. The contacted whole blood or components contain substantially fewer immune suppressive microvesicular particles in comparison to the whole blood or components originally residing in the subject, and the immune suppressive microvesicular particles include exosomes and microvesicles.
The extracorporeal circulation system uses binding agents that include antibodies, proteins, aptamers, or surfaces with selective adhesion to microvesicles, including a surface that selectively restricts microvesicles from passage. Dependent aspects describe agent architectures that apply agents bound to a plurality of objects and capture the objects by filtration prior to returning the contacted blood, as well as hollow-fiber filters with porous hollow-fiber membranes and optional bead retention based on a size range relative to pores.
Claims Coverage
The independent claim covers an extracorporeal circulation method that contacts blood or components with binding agents to remove immune suppressive microvesicular particles and then returns the contacted blood with a substantially reduced particle level; one independent claim is explicitly identified, with dependent claims refining the binding agents and extracorporeal implementation, including filtration capture and hollow-fiber pore constraints.
Extracorporeal circulation for binding and removal of immune suppressive microvesicular particles
A method of removing immune suppressive microvesicular particles from the blood of a subject in need thereof by establishing an extracorporeal circulation system comprising contacting the whole blood or components thereof with a single or plurality of agents capable of binding immune suppressive microvesicular particles found within said blood or components thereof to remove said immune suppressive microvesicular particles from said whole blood or components thereof; and returning said contacted whole blood or components thereof into the original blood, said contacted whole blood or components thereof containing substantially fewer immune suppressive microvesicular particles in comparison to the whole blood or components thereof originally residing in the subject.
Agents bound to objects with filtration capture before returning
The extracorporeal circulation system includes agents bound to a plurality of objects and a filtration step captures the objects within the extracorporeal circulation system before returning the contacted whole blood or components to the subject.
Bead size relative to hollow-fiber pores for retention
Beads have a size range larger than pores of hollow fibers used in extracorporeal systems to restrict bead movement out of the extracorporeal systems.
Binding agents selected from antibody/protein/aptamer/surface modalities
Agents capable of binding immune suppressive microvesicular particles are selected from antibodies, proteins, aptamers, a surface that restricts microvesicles from passage, or a surface with selective adhesion to microvesicles.
Antibody specificity for proteins associated with immune suppression in a cancer patient
Antibodies have specificity for proteins selected from Fas ligand, MHC I, MI-IC II, CD44, placental alkaline phosphatase, TSG-101, MHC I/peptide complexes, MHC II/peptide complexes, and proteins present on the exterior of microvesicles contributing to immune suppression in a cancer patient.
Lectin selection for binding microvesicular particles
A lectin is selected from GNA, NPA, Concanavalin A and cyanovirin.
The claims center on the extracorporeal circulation contact-and-return framework using agents that bind immune suppressive microvesicular particles to produce a substantially reduced particle level in the returned blood. Dependent features specify agent modality, selected antibody targets, lectin selection, and extracorporeal implementation refinements including filtration capture and bead size relative to hollow-fiber pores.
Stated Advantages
Reduces the level of immune suppressive microvesicular particles in blood by returning contacted blood containing substantially fewer immune suppressive microvesicular particles than originally residing in the subject.
Enables removal of immune suppressive microvesicular particles using an extracorporeal circulation system that contacts whole blood or components with binding agents.
Documented Applications
Cancer therapy, including removing immune suppressive microvesicular particles from a cancer patient.
Vaccine adjuvant/neoadjuvant use, as described for cancer vaccination.
Combination with other immune modulators and/or chemotherapy, as described in the provided content.
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