Therapeutic pooled blood apoptotic cell preparations and uses thereof
AssigneeEnlivex Therapeutics RDO Ltd
InventorsDror Mevorach, Shai Novik
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Abstract
Cell preparations comprising a pooled and enriched, mononuclear apoptotic cell population, and a method of preparing this cell preparation are described. The pooled mononuclear apoptotic cell preparation may be obtained from pooled, allogeneic white blood cell fractions that are pooled prior to or following induction of apoptosis. Further, described herein are methods of use of these pooled apoptotic cell preparations for treating an immune disease, an inflammatory disease, an autoimmune disease, or infertility in a subject. For example, a pooled apoptotic cell preparation may be used to treat graft versus host disease (GVHD) in an allogeneic subject.
Claims26
A method of prolonging survival of a subject suffering from an immune disease, an autoimmune disease, a cytokine release syndrome (CRS), a cytokine storm, a cancer, or an inflammatory disease, comprising administering to the subject a pharmaceutical composition comprising an irradiated mononuclear-enriched, early apoptotic cell preparation, wherein said early apoptotic cells are irradiated post induction of apoptosis, and wherein said irradiated mononuclear-enriched, early apoptotic cell preparation comprises
- a decreased number of non-quiescent non-apoptotic cells;
- a suppressed cellular activation of any living non-apoptotic cells;
- or
- a reduced proliferation of any living non-apoptotic cells;
- or any combination thereof compared with a preparation comprising a non-irradiated cell population.
A therapeutic, irradiated, mononuclear, early apoptotic cell preparation comprising a mononuclear-enriched cell population in an early apoptotic state that is irradiated post induction of apoptosis, and wherein said irradiated mononuclear-enriched, early apoptotic cell preparation comprises
- a decreased number of non-quiescent non-apoptotic cells;
- a suppressed cellular activation of any living non-apoptotic cells;
- or
- a reduced proliferation of any living non-apoptotic cells;
- or any combination thereof compared with a preparation comprising non-irradiated cell populations.
A method for producing a pharmaceutical composition comprising an irradiated mononuclear apoptotic cell preparation comprising a mononuclear cell population in an early apoptotic state, said method comprising the following steps,
- (a) obtaining a mononuclear-enriched cell population of peripheral blood;
- (b) freezing said mononuclear-enriched cell population in a freezing medium comprising an anticoagulant;
- (c) thawing said mononuclear-enriched cell population;
- (d) incubating said mononuclear-enriched cell population in an apoptosis inducing incubation medium comprising methylprednisolone at a final concentration of about 10-100 μg/mL and an anticoagulant, wherein induction produces an early apoptotic cell population;
- (e) resuspending said induced early apoptotic cell populations obtained in step (d) in an administration medium;
- and
- (f) inactivating said early apoptotic cell populations from step (e), wherein said inactivation comprises irradiating said apoptotic cell populations from step (e), and wherein said irradiation comprises gamma irradiation or UV irradiation at about 20-60 Grey units (Gy);
- wherein said method produces a pharmaceutical composition comprising an irradiated mononuclear apoptotic cell preparation, wherein said irradiated mononuclear-enriched, early apoptotic cell preparation comprises
- a decreased number of non-quiescent non-apoptotic cells;
- a suppressed cellular activation of any living non-apoptotic cells;
- or
- a reduced proliferation of any living non-apoptotic cells;
- or any combination thereof compared with a preparation comprising non-irradiated cell populations.
Dependencies are inferred from the claim text.