USE OF IL-2R-BETA-GAMMA AGONIST PEPTIDES IN CELL MANUFACTURING
The use of IL-2Rβγc agonist peptides in cell manufacturing is disclosed. The IL-2Rβγc agonist peptides can facilitate the selective growth of immune cell populations. Culture media comprising the IL-2Rβγc agonist peptides, methods of expanding a target immune cell population, and methods of manufacturing a target immune cell population are disclosed. The enriched immune cell populations can be used in immunotherapy.
1 . A culture medium for expanding a target immune cell population comprising a first stimulant of proliferation for the target immune cell population proliferation, wherein the first stimulant comprises an IL-2Rβγc agonist peptide, wherein the IL-2Rβγc agonist peptide comprises:
(a) an IL-2Rβ ligand, wherein the IL-2Rβ ligand comprises:
an amino acid sequence of any one of SEQ ID NO: 134, 527, 591, 598, 755, 756, 760, 761, 765, 766, 770, 776, and 777; or
an amino acid sequence having greater than 80% sequence similarity to any one of SEQ ID NO: 134, 527, 591, 598, 755, 756, 760, 761, 765, 766, 770, 776, and 777; and
(b) an IL-2Rγc ligand, wherein the IL-2Rγc ligand comprises:
an amino acid sequence of any one of SEQ ID NO: 652, 786-788, 791, 792, and 795; or
an amino acid sequence having greater than 80% sequence similarity to any one of SEQ ID NO: 652, 786-788, 791, 792, and 795.
2 . The culture medium of claim 1 , wherein the IL-2Rβ ligand comprises SEQ ID NO: 134.
3 . The culture medium of claim 1 , wherein the IL-2Rβ ligand comprises an amino acid sequence having greater than 80% sequence similarity to SEQ ID NO: 134.
4 . The culture medium of claim 1 , wherein the IL-2Rβ ligand comprises SEQ ID NO: 527.
5 . The culture medium of claim 1 , wherein the IL-2Rβ ligand comprises an amino acid sequence having greater than 80% sequence similarity to SEQ ID NO: 527.
6 . The culture medium of claim 1 , wherein the IL-2Rγc ligand comprises SEQ ID NO: 652.
7 . The culture medium of claim 1 , wherein the IL-2Rγc ligand comprises an amino acid sequence having greater than 80% sequence similarity to SEQ ID NO: 652.
8 . The culture medium of claim 1 , wherein the IL-2Rβ ligand is bound to the IL-2Rγc ligand through a ligand linker.
9 . The culture medium of claim 8 , wherein the ligand linker comprises a peptidyl ligand linker.
10 . The culture medium of claim 1 , wherein the IL-2Rβγc agonist peptide comprises any one of SEQ ID NO: 801-804 and 809-812, 829-830, 833, 834, 839, and 844-852, wherein X 300 is selected from any one of SEQ ID NO: 1-39.
11 . The culture medium of claim 1 , wherein the IL-2Rβγc agonist peptide comprises any one of SEQ ID NO: 801-804.
12 . The culture medium of claim 1 , wherein the IL-2Rβγc agonist peptide comprises an amino acid sequence having greater than 80% sequence similarity to any one of SEQ ID NO: 801-804, 829-830, 833, 834, 839, and 844-852, wherein X 300 is selected from any one of SEQ ID NO: 1-39.
13 . The culture medium of claim 1 , wherein the IL-2Rβγc agonist peptide comprises any one of SEQ ID NO: 801 and 802.
14 . The culture medium of claim 1 , wherein the IL-2Rβγc agonist peptide comprises any one of SEQ ID NO: 834, 839, and 844-852, wherein X 400 is selected from any one of SEQ ID NO: 1-39.
15 . The culture medium of claim 1 , wherein the IL-2Rβγc agonist peptide comprises an amino acid sequence having greater than 80% sequence similarity to any one of SEQ ID NO: 834, 839, and 844-852, wherein X 400 is selected from any one of SEQ ID NO: 1-39.
16 . The culture medium of claim 1 , wherein the IL-2Rβγc agonist peptide comprises any one of SEQ ID NO: 851 and 852.
17 . The culture medium of claim 1 , wherein the IL-2Rβγc agonist peptide is immobilized.
18 . The culture medium of claim 1 , wherein the culture medium comprises a second stimulant of proliferation for the target immune cell population.
19 . The culture medium of claim 18 , wherein the second stimulant comprises an IL-7Rαγc agonist peptide, an IL-15Rβγc agonist peptide, or a combination thereof.
20 . The culture medium of claim 1 , wherein the culture medium comprises an antibody directed to the target immune cell population.
21 . An enriched population of immune cells prepared using the culture medium of claim 1 .
22 . A method of expanding a target immune cell population of an initial immune cell population, comprising incubating an initial immune cell population in the culture medium of claim 1 to provide an expanded target immune cell population.
23 . An expanded population of immune cells prepared using the method of claim 22 .
24 . A pharmaceutical composition comprising the expanded population of immune cells of claim 23 .
25 . A method of treating a disease in a patient comprising administering to a patient in need of such treatment a therapeutically effective amount of the pharmaceutical composition of claim 24 .