Tumor suppression using human placental perfusate and human placenta-derived intermediate natural killer cells
US-9216200-B2 · Dec 22, 2015 · US
US2016235790A1 · US · A1
| Field | Value |
|---|---|
| Publication number | US-2016235790-A1 |
| Application number | US-201415026896-A |
| Country | US |
| Kind code | A1 |
| Filing date | Oct 2, 2014 |
| Priority date | Oct 3, 2013 |
| Publication date | Aug 18, 2016 |
| Grant date | — |
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Provided herein are methods of treatment comprising administering to a subject, e.g., a human subject, mononuclear cells from human placental perfusate and hematopoietic cells, and compositions comprising them, and their uses to establish chimerism, engraft tissue (e.g., blood), reduce the severity or duration of graft versus host disease, and treat or ameliorate symptoms of metabolic disorders and hematologic disorders, such as hematologic malignancies.
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What is claimed: 1 . A method of transplanting human umbilical cord blood (UCB) cells to a subject, said method comprising administering UCB cells in combination with a population of mononuclear cells from human placental perfusate, wherein said UCB cells are not related to the subject. 2 . A method of transplanting human umbilical cord blood (UCB) cells to a subject, said method comprising administering UCB cells in combination with a population of mononuclear cells from human placental perfusate, wherein said cells from human placental perfusate are not related to the subject. 3 . A method of transplanting human umbilical cord blood (UCB) cells to a subject, said method comprising administering UCB cells in combination with a population of mononuclear cells from human placental perfusate, wherein said cells from human placental perfusate are not matched to the subject. 4 . The method of claim 1 , 2 , or 3 , wherein said UCB cells are not related to said mononuclear cells from placental perfusate. 5 . The method of claim 1 , 2 , or 3 , wherein said UCB cells are not matched to said mononuclear cells from placental perfusate. 6 . The method of claim 1 , 2 , or 3 , wherein said UCB cells are not related or matched to said mononuclear cells from placental perfusate. 7 . The method of any of claims 1 - 6 , wherein said UCB cells are 3/6 to 6/6 HLA-matched to the subject. 8 . The method of any of claims 1 - 7 , wherein one unit of UCB cells is administered. 9 . The method of any of claims 1 - 7 , wherein greater than one unit of UCB cells is administered. 10 . The method of claim 9 , wherein 2-6 units of UCB cells are administered. 11 . The method of any of claims 1 - 10 , wherein said UCB cells are present in UCB. 12 . The method of any of claims 1 - 11 , wherein said mononuclear cells from placental perfusate are present in placental perfusate. 13 . The method of any of claims 1 - 12 , wherein the placental perfusate is obtained from a placenta that has been partially exsanguinated. 14 . The method of any of claims 1 - 13 , wherein 2% or greater of the placental perfusate cells are CD34+. 15 . The method of any of claims 1 - 14 , wherein said method results in chimerism in the subject. 16 . The method of claim 15 , said chimerism comprising UCB cells or progeny therefrom. 17 . The method of claim 15 or 16 , said chimerism comprising UCB cells or progeny therefrom and placental perfusate cells or progeny therefrom. 18 . The method of any of claims 15 - 17 , wherein greater than one unit of UCB cells is administered and wherein said method results in chimerism in the subject, said chimerism comprising cells from greater than one unit of UCB cells or progeny therefrom. 19 . The method of any of claims 15 - 18 , said chimerism comprising placental perfusate cells or progeny therefrom. 20 . The method of any of claims 1 - 19 , wherein said method results in engraftment of UCB cells. 21 . The method of any of claims 1 - 20 , wherein said method results in engraftment of placental perfusate cells. 22 . The method of any of claims 1 - 21 , wherein said method reduces the duration or severity of graft versus host disease. 23 . The method of any of claims 1 - 22 , wherein said subject has a tumor and said method results in a graft versus tumor reaction. 24 . The method of any of claims 1 - 21 , wherein said method results in amelioration of a symptom of a metabolic disorder such as adrenoleukodystrophy, mucopolysaccharidosis, Niemann-Pick disease, metachromatic leukodystrophy, Wolman disease, Krabbe's disease, Gaucher's disease, fucosidosis, or Batten disease in a subject in need thereof. 25 . The method of any of claims 1 - 21 , wherein said method results in amelioration of a symptom of a hematologic disorder or malignancy, such as myelodysplastic syndrome, amegakaryocytic thrombocytopenia, acute lymphoblastic leukemia, acute myelogenous leukemia, sickle cell disease, beta thalassemia, severe combined immunodeficiency disease, marrow failure, or anemia such as severe aplastic anemia or Diamond-Blackfan anemia in a subject in need thereof. 26 . The method of any one of claims 1 - 25 , wherein the subject is a human subject. 27 . The method of claim 26 , wherein the human subject is 25 years old or younger. 28 . The method of claim 27 , wherein the human subject is an infant. 29 . A method of transplanting hematopoietic cells to a subject, comprising administering the hematopoietic cells in combination with mononuclear cells from human placental perfusate, e.g., human placental perfusate. 30 . The method of claim 29 , wherein said hematopoietic cells are bone marrow or cells therefrom, peripheral blood or cells therefrom, or umbilical cord blood or cells therefrom. 31 . Hematopoietic cells for use in a method of treatment of a disease in a subject, wherein the method comprises administering said hematopoietic cells in combination with mononuclear cells from human placental perfusate, wherein the disease is a metabolic disorder or a symptom thereof; a hematologic disorder or malignancy or a symptom thereof; graft versus host disease; or a tumor. 32 . The hematopoietic cells for use of claim 31 , wherein said hematopoietic cells are bone marrow or cells therefrom, peripheral blood or cells therefrom, or umbilical cord blood or cells therefrom. 33 . The hematopoietic cells for use of claim 32 , wherein said umbilical cord blood cells are not related to the subject, or wherein said mononuclear cells from human placental perfusate are not related to the subject, or wherein said mononuclear cells from human placental perfusate are not matched to the subject. 34 . The hematopoietic cells for use of claim 33 , wherein the method is as defined in claims 4 to 28 .
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