PLACENTA-DERIVED ALLOGENEIC CAR-T CELLS AND USES THEREOF
The present invention discloses populations of T cells expressing a chimeric antigen receptor (CAR), wherein said T cells are placental T cells derived from cord blood, placental perfusate, or a mixture thereof. Such populations of cells are shown to be improved in a number of aspects over alternative populations of cells such as those derived from peripheral blood mononuclear cell T cells. It also discloses methods of treating cancer, such as a hematologic cancer, e.g., a B cell cancer, or a symptom thereof in a patient in need thereof. These methods comprise administering to the patient an amount of the population of T cells of any one of the invention effective to alleviate the cancer or symptom thereof in the patient.
1 . A population of T cells expressing a chimeric antigen receptor (CAR), wherein said T cells are placental T cells.
2 . The population of T cells of claim 1 , wherein said placental T cells are cord blood T cells, placental perfusate T cells, or a mixture thereof.
3 . The population of T cells of claim 1 , wherein said placental T cells are cord blood T cells.
4 . The population of T cells of claim 1 , wherein said placental T cells are a mixture of cord blood T cells and placental perfusate T cells.
5 . The population of T cells of any one of claims 1 - 4 , wherein said CAR has been introduced to the cell by transfection.
6 . The population of T cells of any one of claims 1 - 4 , wherein said CAR has been introduced to the cell by viral transduction.
7 . The population of T cells of claim 6 , wherein said CAR has been introduced to the cell by viral transduction with a retroviral vector.
8 . The population of T cells of claim 6 , wherein said CAR has been introduced to the cell by viral transduction with a lentiviral vector.
9 . The population of T cells of any one of claims 1 - 8 , wherein said population of T cells has a greater percentage of cells expressing CD45RA than a population of peripheral blood mononuclear cell T cells.
10 . The population of T cells of any one of claims 1 - 9 , wherein said population of T cells has a greater percentage of cells expressing CD27 than a population of peripheral blood mononuclear cell T cells.
11 . The population of T cells of any one of claims 1 - 10 , wherein said population of T cells has a greater percentage of cells expressing CCR7 than a population of peripheral blood mononuclear cell T cells.
12 . The population of T cells of any one of claims 1 - 11 , wherein said population of T cells has a greater percentage of cells expressing CD127 than a population of peripheral blood mononuclear cell T cells.
13 . The population of T cells of any one of claims 1 - 12 , wherein said population of T cells has a lower percentage of cells expressing CD57 than a population of peripheral blood mononuclear cell T cells.
14 . The population of T cells of any one of claims 1 - 13 , wherein said population of T cells has a greater percentage of cells expressing CD62L than a population of peripheral blood mononuclear cell T cells.
15 . The population of T cells of any one of claims 1 - 14 , wherein said population of T cells has a lower percentage of cells expressing CD25 than a population of peripheral blood mononuclear cell T cells.
16 . The population of T cells of any one of claims 1 - 15 , wherein said population of T cells has a greater percentage of cells expressing Lag-3+ than a population of peripheral blood mononuclear cell T cells.
17 . The population of T cells of any one of claims 1 - 16 , wherein said population of T cells has a lower percentage of cells expressing Tim-3 than a population of peripheral blood mononuclear cell T cells.
18 . The population of T cells of any one of claims 1 - 17 , wherein said population of T cells exhibit greater in vitro killing of a cancer cell line than a population of peripheral blood mononuclear cell T cells.
19 . The population of T cells of any one of claims 1 - 18 , wherein said population of T cells express a greater amount of perforin in an in vitro challenge against a cancer cell line than a population of peripheral blood mononuclear cell T cells.
20 . The population of T cells of any one of claims 1 - 19 , wherein said population of T cells express a greater amount of GM-CSF in an in vitro challenge against a cancer cell line than a population of peripheral blood mononuclear cell T cells.
21 . The population of T cells of any one of claims 1 - 20 , wherein said population of T cells express a greater amount of TNF-a in an in vitro challenge against a cancer cell line than a population of peripheral blood mononuclear cell T cells.
22 . The population of T cells of any one of claims 1 - 21 , wherein said population of T cells express a greater amount of IL-2 in an in vitro challenge against a cancer cell line than a population of peripheral blood mononuclear cell T cells.
23 . The population of T cells of any one of claims 1 - 22 , wherein said population of T cells express a greater amount of granzyme B in an in vitro challenge against a cancer cell line than a population of peripheral blood mononuclear cell T cells.
24 . The population of T cells of any one of claims 1 - 23 , wherein said population of T cells produces increased survival in an in vivo cancer model than a population of peripheral blood mononuclear cell T cells.
25 . The population of T cells of any one of claims 1 - 24 , wherein said population of T cells produces decreased body weight loss in an in vivo cancer model than a population of peripheral blood mononuclear cell T cells.
26 . The population of T cells of any one of claims 1 - 25 , wherein said population of T cells produces decreased graft versus host disease (GvHD) in an in vivo cancer model than a population of peripheral blood mononuclear cell T cells.
27 . The population of T cells of any one of claims 9 - 26 , wherein said population of peripheral blood mononuclear cell T cells also expresses a said CAR.
28 . The population of T cells of claim 27 , wherein said CAR has been introduced to said population of peripheral blood mononuclear cell T cells by transfection.
29 . The population of T cells of claim 27 , wherein said CAR has been introduced to said population of peripheral blood mononuclear cell T cells by viral transduction.
30 . The population of T cells of claim 29 , wherein said CAR has been introduced to said population of peripheral blood mononuclear cell T cells by viral transduction with a retroviral vector.
31 . The population of T cells of claim 29 , wherein said CAR has been introduced to said population of peripheral blood mononuclear cell T cells by viral transduction with a lentiviral vector.
32 . The population of T cells any one of claims 1 - 31 , wherein said CAR which has been introduced to said population of peripheral blood mononuclear cell T cells is the same CAR expressed by said population of T cells.
33 . The population of T cells any one of claims 1 - 32 , wherein said population of T cells comprises a further genetic alteration to reduce immunogenicity against a host.
34 . The population of T cells claim 33 , wherein said genetic alteration is a gene knockout.
35 . The population of T cells claim 34 , wherein said gene knockout is a T cell receptor (TCR) knockout.
36 . The population of T cells claim 34 , wherein said gene knockout is a T cell receptor alpha constant (TRAC) knockout.
37 . The population of T cells any one of claims 33 - 36 , wherein said further genetic alteration is effected by transfection, retroviral transduction, or lentiviral transduction.
38 . The population of T cells any one of claims 33 - 36 , wherein said further genetic alteration is effected by the use of CRISPR, talen, or zn finger technology.
39 . A method of treating cancer or a symptom thereof in a patient in need thereof, the method comprising the step of administering to the patient an amount of the population of T cells of any one of claims 1 - 38 effective to alleviate the cancer or symptom thereof in the patient.
40 . The method of claim 39 , wherein said cancer is a hematologic cancer.
41 . The method of claim 40 , wherein said hematologic cancer is a B cell cancer.
42 . The method of any one of claims 39 - 41 , wherein the population of T cells are allogeneic to said patient.