Immunomodulatory properties of multipotent adult progenitor cells and uses thereof
Inventors
Maziarz, Richard • Kovacsovics, Magdalena • Streeter, Philip • Deans, Robert • Van't Hof, Wouter
Assignees
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Publication Number
US-11197889-B2
Publication Date
2021-12-14
Expiration Date
Abstract
Isolated cells are described that are not embryonic stem cells, not embryonic germ cells, and not germ cells. The cells can differentiate into at least one cell type of each of at least two of the endodermal, ectodermal, and mesodermal lineages. The cells do not provoke a harmful immune response. The cells can modulate immune responses. As an example, the cells can suppress an immune response in a host engendered by allogeneic cells, tissues, and organs. Methods are described for using the cells, by themselves or adjunctively, to treat subjects. For instance, the cells can be used adjunctively for immunosuppression in transplant therapy. Methods for obtaining the cells and compositions for using them also are described.
Core Innovation
The invention relates to a method of ameliorating an immune dysfunction in a subject by administering mammalian multipotent adult progenitor cells that are not embryonic stem cells, embryonic germ cells, or germ cells. The administered cells are allogeneic to the subject and characterized by expression of telomerase and a normal karyotype.
The cells have undergone at least 10-40 cell doublings in culture and are administered adjunctively to one or more other treatments. The cells are not genetically engineered to improve their immunological properties, and the immune dysfunction is not GVHD and is not diabetes.
The multipotent adult progenitor cells are described as differentiating across at least two germ layers and as exhibiting low immunogenicity with immunomodulatory/immunosuppressive effects. The document frames the approach in immune dysfunction settings including allogeneic contexts intended to mitigate HVG and GVHD-related immune responses.
Claims Coverage
The patent includes one independent claim directed to a method of ameliorating an immune dysfunction in a human using specifically characterized allogeneic multipotent adult progenitor cells as an adjunct to other treatments. Across the claim set, the immune dysfunction is constrained to exclude GVHD and diabetes, and dependent claims further refine dose, route, source, and optional co-administration features.
Adjunctive administration of non-embryonic, allogeneic MAPCs to ameliorate immune dysfunction
Administering to a human subject mammalian multipotent adult progenitor cells that are not embryonic stem cells, embryonic germ cells, or germ cells, are allogeneic to the subject, express telomerase, have a normal karyotype, and have undergone at least 10-40 cell doublings in culture, wherein the cells are administered adjunctively to one or more other treatments, the cells have not been genetically engineered to improve their immunological properties, and said immune dysfunction is not GVHD and is not diabetes.
Cell dose range per subject mass
Administering the progenitor cells to the subject in one or more doses at a dosage of 10^4 to 10^8 cells per kilogram of the subject’s mass.
Sub-range dosing within the cell-per-kilogram range
Administering progenitor cells to a subject in one or more doses at a dose level of 10^6 to 10^7 progenitor cells per kilogram of the subject’s mass.
Intravenous infusion administration route
Administering progenitor cells to a subject by intravenous infusion.
Deriving MAPCs from specified source tissues or bodily fluids
Deriving progenitor cells from cells isolated from one or more specified tissues or bodily fluids, including placental tissue, umbilical cord tissue, umbilical cord blood, bone marrow, blood, spleen tissue, thymus tissue, spinal cord tissue, adipose tissue, and liver tissue.
Adjunctive co-administration of antimicrobial and antiviral agents
Administering in combination one or more of an antibiotic agent, an anti-fungal agent, and/or an anti-viral agent to the subject.
Overall, claim coverage centers on using non-embryonic, allogeneic multipotent adult progenitor cells as an adjunct to other treatments without genetic engineering to improve immunological properties, to ameliorate an immune dysfunction explicitly excluding GVHD and diabetes. Dependent claims further specify dose ranges, an intravenous infusion route, acceptable sources for deriving the cells, and optional co-administration of antibiotic, anti-fungal, and anti-viral agents.
Stated Advantages
Ameliorating an immune dysfunction in a subject.
Immunomodulatory/immunosuppressive effects in described immune contexts.
Low immunogenicity of the multipotent adult progenitor cells.
Mitigation of immune responses in allogeneic settings described in relation to HVG/GVHD.
Documented Applications
Transplant immunosuppression/allogeneic settings in which the described immune responses are intended to be mitigated, with the immune dysfunction in the method constrained to not be GVHD.
Administration for immune dysfunctions with the immune dysfunction constrained to not be GVHD and not be diabetes.
Use as adjunctive therapy in combination with other treatments, including optional administration of antibiotic, anti-fungal, and anti-viral agents.
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