JP-2022513113-A5 -

Dates

Publication Date

20221206

Application Date

20191126

Description

Equivalents Those skilled in the art will be able to recognize or confirm many equivalents of the specific embodiments described herein by means of mere conventional experimentation. Such equivalents are intended to be covered by the following claims. The present invention provides, for example, the following items. (Item 1) A composition suitable for implantation into a host, (a) a first cell population comprising parenchymal cells, endothelial cells, or a combination thereof, wherein the cells of the first population are not genetically modified; and (b) A second cell population comprising genetically modified immunomodulatory cells that inhibit the immune response against the first cell population. A composition containing the following: (Item 2) The composition according to item 1, wherein the first cell population includes parenchymal cells. (Item 3) The composition according to item 1 or 2, wherein the parenchymal cells in the first cell population are hepatocytes, pancreatic exocrine cells, myocytes, pancreatic endocrine cells, neurons, intestinal cells, adipocytes, spleen cells, renal cells, cholangiocarcinomas, Kupffer cells, stellate cells, cardiomyocytes, alveolar cells, bronchocytes, club cells, urothelial cells, mucinous cells, parietal cells, chief cells, G cells, goblet cells, enteroendocrine cells, Paneth cells, M cells, tufted cells, glial cells, gallbladder cells, keratinocytes, melanocytes, Merkel cells, Langerhans cells, osteocytes, osteoclasts, esophageal cells, photoreceptor cells, or corneal epithelial cells. (Item 4) The composition according to any one of the preceding items, wherein the first cell population includes endothelial cells. (Item 5) The composition according to item 4, wherein the endothelial cells in the first cell population are umbilical vein endothelial cells, liver endothelial cells, brain endothelial cells, lung endothelial cells, kidney endothelial cells, heart endothelial cells, spleen endothelial cells, testicular endothelial cells, lymph endothelial cells, or bone marrow endothelial cells. (Item 6) The composition according to any one of the preceding items, wherein the second cell population includes genetically modified non-parenchymal cells. (Item 7) The composition according to item 6, wherein the genetically modified non-parenchymal cells are stromal cells. (Item 8) The composition according to item 7, wherein the genetically modified stromal cells are endothelial cells, fibroblasts, or pericytes. (Item 9) The composition according to item 7, wherein the genetically modified stromal cells are pluripotent stromal cells. (Item 10) The composition according to item 9, wherein the genetically modified pluripotent stromal cells are derived from bone marrow. (Item 11) The composition according to item 9, wherein the genetically modified pluripotent stromal cells are derived from non-bone marrow tissue. (Item 12) The composition according to any one of the preceding items, wherein the second population comprises genetically modified endothelial cells. (Item 13) The composition according to item 12, wherein the genetically modified endothelial cells are umbilical vein endothelial cells, liver endothelial cells, brain endothelial cells, lung endothelial cells, kidney endothelial cells, heart endothelial cells, spleen endothelial cells, testicular endothelial cells, lymph endothelial cells, or bone marrow endothelial cells. (Item 14) The composition according to any one of the preceding items, wherein the cells of the second cell population are genetically engineered to express proteins that activate one or more checkpoint pathways to induce immune cell exhaustion and anergy against cells present in the first cell population. (Item 15) The composition according to item 14, wherein the cells of the second cell population are genetically engineered to express immune checkpoint proteins. (Item 16) The composition according to item 15, wherein the immune checkpoint protein is PD-1, PD-L1, PDL-2, CD47, CD39, CD73, CD200, HVEC, CEACAM1, CD155, TIM-3, LAG-3, CTLA-4, A2AR, B7-H3, B7-H4, HLA-E, BTLA, IDO, KIR, VISTA, or a combination thereof. (Item 17) The composition according to item 16, wherein the immune checkpoint protein is PD-L1, CD47, HLA-E, CD39, CD73, or a combination thereof. (Item 18) The composition according to any one of items 14 to 17, wherein the genetically modified cells of the second cell population include a vector for expressing the protein. (Item 19) The composition according to item 18, wherein the vector is a viral vector. (Item 20) The composition according to item 19, wherein the viral vector is a lentivirus, vaccinia virus, poliovirus, adenovirus, adeno-associated virus, SV40, herpes simplex virus, or retrovirus. (Item 21) The composition according to item 20, wherein the virus is a lentivirus. (Item 22) The composition according to any one of items 18 to 21, wherein the expression of the protein is under the control of a constitutively active pr