JPWO2021203061A5 - - Google Patents

Claims (30)

1. A composition for use in a method of treating COVID-19 in a subject in need thereof, the method comprising administering to the subject hematopoietic stem cells in an amount effective to treat the disease. 10. The composition of claim 1, wherein the method further comprises administering a programmed death 1 (PD-1) antagonist. The composition of claim 2, wherein the PD-1 antagonist is an agent that binds to and antagonizes programmed death 1 (PD-1). The composition of claim 3, wherein the agent that binds to and antagonizes PD-1 is a peptide that binds to PD-1. The composition of claim 3, wherein the agent that binds to and antagonizes PD-1 is a humanized antibody that selectively binds to PD-1. The composition of claim 5, wherein the humanized antibody that selectively binds to PD-1 is nivolumab, pembrolizumab, pidilizumab, MEDI-0680, REGN2810, or AMP-224. The composition of claim 6, wherein the humanized antibody that selectively binds to PD-1 is nivolumab. The composition of any of claims 1 to 7, wherein the method further comprises administering to the subject a hematopoietic stem cell mobilizing agent. 9. The composition of claim 8, wherein the mobilizing agent is granulocyte colony-stimulating factor (G-CSF), pegylated G-CSF (pegfilgrastim), lenograstim, a glycosylated form of G-CSF, C-X-C motif chemokine 2 (CXCL2), C-X-C chemokine receptor type 4 (CXCR-4), or plerixafor . The composition of any one of claims 2 to 9, wherein the PD-1 antagonist is administered separately in time or simultaneously with the hematopoietic stem cells. The composition of any of claims 1 to 10, wherein the PD-1 antagonist is administered simultaneously, within 1 day, within 1 week, within 1 month, within 2 months, within 3 months, within 4 months, within 5 months, or within 6 months of administration of the hematopoietic stem cells . The composition of claim 8 or 9, wherein the PD-1 antagonist is administered simultaneously, within one day, within one week, within one month, within two months, within three months, within four months, within five months, or within six months of administration of the hematopoietic stem cell mobilizing agent . The composition of any one of claims 2 to 12, wherein the PD-1 antagonist is administered intravenously or subcutaneously. The composition of any one of claims 1 to 13, wherein the hematopoietic stem cells are administered intravenously. The composition of any one of claims 8, 9, or 12-14, wherein the hematopoietic stem cell mobilizing agent is administered intravenously, intradermally, or subcutaneously. The source of hematopoietic stem cells may be bone marrow, bone marrow lineage-depleted cells (lin-), cKit+ purified lineage-negative bone marrow-derived cells, Sca+ purified lineage-negative bone marrow-derived cells, cKit+Sca+ purified bone marrow-derived cells, mobilized from host bone marrow using GM-CSF, G-CSF, mobilized from host bone marrow using AMD3100, plerixafor, or the molecule 1,1'-[1,4-phenylenebis(methylene)]bis[1,4,8,11-tetraazacyclotetradecane], umbilical cord blood or umbilical cord blood. The composition of any of claims 1 to 15, which is derived from a human subject, unselected umbilical cord blood stem cells (UCBSCs) or UCBSCs selected for CD34+ cells, CCR2+, or lin(-) cells, human leukocyte antigen (HLA)-matched blood, mesenchymal stem cells derived from blood or bone marrow, hematopoietic stem cells differentiated from induced pluripotent stem cells, mobilized peripheral blood, peripheral blood, hematopoietic stem cell subsets comprising lin- cells purified with the CCR2+ marker, lineage -negative purified peripheral blood, or CD34+ enriched peripheral blood. The composition according to any one of claims 1 to 16, wherein the source of the hematopoietic stem cells is bone marrow, peripheral blood, umbilical cord blood, or induced pluripotent stem cells. The composition according to any one of claims 1 to 17, wherein the source of the hematopoietic stem cells is autologous. The composition of any one of claims 1 to 17, wherein the source of hematopoietic stem cells is allogeneic, the donor cells being HLA-matched to the recipient. 19. The composition of any one of claims 1 to 18, wherein a sample containing hematopoietic stem cells is obtained from a subject and treated in vitro to expand the number of stem cells in the sample prior to administering the hematopoietic stem cells to the subject. 19. The composition of any one of claims 1 to 18, wherein a sample containing hematopoietic stem cells is obtained from a subject and treated in vitro to increase the percentage of stem cells in the sample prior to administering the hematopoietic stem cells to the subject. 22. The composition of any of claims 1-21, wherein at least 5, 10, 15, 20, 25, 30, 35, 40, 45, or 50 percent of the hematopoietic stem cells are CCR2 positive (CCR2+), CD34 positive (CD34+), and/or lineage negative (lin-) cells. 23. The composition of any of claims 1 to 22, wherein the hematopoietic stem cells for administration to a subject are enriched ex vivo for CCR2 positive (CCR2+) cells, CD34 positive (CD34+) cells and/or lineage negative (lin-) cells prior to administration to the subject. The composition of any of claims 1 to 23, wherein the hematopoietic stem cells are treated ex vivo to deplete CCR2 negative (CCR2-) cells prior to administration to the subject. The composition of any one of claims 1 to 24, wherein the COVID-19 is severe COVID-19. 1. A composition for use in a method of treating COVID-19 in a subject in need thereof, the method comprising administering to the subject a hematopoietic stem cell mobilizing agent in an amount effective to treat the disease. 27. The composition of claim 26, wherein the mobilizing agent is granulocyte colony-stimulating factor (G-CSF), pegylated G-CSF (pegfilgrastim), lenograstim, a glycosylated form of G-CSF, C-X-C motif chemokine 2 (CXCL2), C-X-C chemokine receptor type 4 (CXCR-4), or plerixafor . 28. The composition of claim 26 or 27, wherein the method further comprises administering a programmed death 1 (PD-1) antagonist. The composition of any one of claims 26 to 28, wherein the method further comprises administering hematopoietic stem cells. 1. A composition for use in a method of treating COVID-19 in a subject in need thereof, the method comprising administering to the subject a hematopoietic stem cell mobilizing agent, harvesting hematopoietic stem cells from the subject, enriching the harvested stem cells for CCR2 positive (CCR2+), CD34 positive (CD34+), or lineage negative (lin-) cells, optionally depleting the harvested stem cells or CCR2- cells , administering the enriched harvested stem cells to the subject, and administering to the subject a PD-1 antagonist.