Tumor suppression using human placental perfusate and human placenta-derived intermediate natural killer cells

Abstract

Provided herein are placental perfusate, placental perfusate cells, and placenta-derived intermediate natural killer cells, and combinations thereof. Also provided herein are compositions comprising the same, and methods of using placental perfusate, placental perfusate cells, and placenta-derived intermediate natural killer cells, and combinations thereof, to suppress the growth or proliferation of tumor cells, cancer cells, and the like, and to treat individuals having tumor cells.

1 .- 28 . (canceled) 
     
     
         29 . A pharmaceutical composition for suppressing the proliferation of tumor cells, the composition comprising a therapeutically effective amount of human placental perfusate cells, wherein said placental perfusate cells comprise CD56 +  placental intermediate natural killer cells. 
     
     
         30 . The pharmaceutical composition of  claim 29 , wherein the composition comprises CD56 + CD16 −  placental intermediate natural killer cells. 
     
     
         31 . The pharmaceutical composition of  claim 30 , wherein the CD56 + CD16 −  placental intermediate natural killer cells comprise at least 50% of the placental perfusate cells. 
     
     
         32 . The pharmaceutical composition of  claim 29 , wherein the composition further comprises CD56+CD16 +  natural killer cells. 
     
     
         33 . The pharmaceutical composition of  claim 31 , wherein the CD56+CD16 +  natural killer cells comprise at least 50% of the cells in the composition. 
     
     
         34 . The pharmaceutical composition of  claim 31 , wherein the CD56+CD16 +  natural killer cells are obtained from one or more of the group consisting of umbilical cord blood, peripheral blood, and bone marrow. 
     
     
         35 . The pharmaceutical composition of  claim 31 , wherein the CD56+CD16 +  natural killer cells and the placental intermediate natural killer cells are obtained from the same individual. 
     
     
         36 . The pharmaceutical composition of  claim 31 , wherein the CD56+CD16 +  natural killer cells are obtained from an intended recipient of the pharmaceutical composition. 
     
     
         37 . The pharmaceutical composition of  claim 29 , wherein the placental intermediate natural killer cells express one or more of the microRNAs hsa-miR-100, hsa-miR-127, hsa-miR-211, hsa-miR-302c, hsa-miR-326, hsa-miR-337, hsa-miR-497, hsa-miR-512-3p, hsa-miR-515-5p, hsa-miR-517b, hsa-miR-517c, hsa-miR-518a, hsa-miR-518e, hsa-miR-519d, hsa-miR-520g, hsa-miR-520h, hsa-miR-564, hsa-miR-566, hsa-miR-618, or hsa-miR-99a at a detectably higher level than peripheral blood natural killer cells. 
     
     
         38 . The pharmaceutical composition of  claim 29 , wherein the placental intermediate natural killer cells express one or more of aminopeptidase N protein, apolipoprotein E protein, atrophin-1 interacting protein 1, innexin inx-3 protein, integrin alpha-2 precursor protein, integrin beta-5 precursor, mast cell surface glycoprotein GP49B precursor protein, or ryanodine receptor 1 protein; and do not express one or more of fibroblast growth factor receptor 4 precursor protein, immunity-associated nucleotide 4-like protein, integrin alpha-L precursor protein, integrin beta 2 precursor protein, integrin beta 4 precursor protein, membrane-bound lytic murein transglycosylase D precursor protein, oxysterol binding protein-related protein 8, or perforin 1 precursor 1 protein. 
     
     
         39 . The pharmaceutical composition of  claim 29 , wherein the pharmaceutical composition further comprises an anti-cancer agent. 
     
     
         40 . The pharmaceutical composition of  claim 29 , wherein the placental perfusate cells are from two or more placentas. 
     
     
         41 . The pharmaceutical composition of  claim 29 , wherein the placental perfusate cells have been contacted with an immunomodulatory compound for a time and in a concentration sufficient for the placental perfusate cells to demonstrate detectably increased cytotoxicity towards tumor cells compared to an equivalent number of placental perfusate cells not contacted with the immunomodulatory compound. 
     
     
         42 . The pharmaceutical composition of  claim 41 , wherein the immunomodulatory compound is lenalidomide or pomalidomide. 
     
     
         43 . The pharmaceutical composition of  claim 29 , wherein the composition further comprises a matrix, a hydrogel, or a scaffold. 
     
     
         44 . The pharmaceutical composition of  claim 43 , wherein the matrix comprises an amniotic membrane material.