Cell therapy compositions and methods of use thereof
The present disclosure provides compositions of immune cells presenting a target molecule or a fragment thereof and provides compositions and methods of producing immune cell therapies with targeted activity against cancer. Methods for conditioning a subject receiving the immune cell therapy of the disclosure are additionally disclosed. The immune cell therapies of the present disclosure can be administered to a subject in need thereof for diseases such as cancer.
1. A method of expanding a CD20 antigen specific cell, the method comprising:
contacting a first cell with a feeder cell in a co-culture comprising a population of allogeneic tumor cell membrane extracts to produce the CD20 antigen specific cell from the first cell,
wherein the feeder cell presents a recombinant CD20 selected from the group consisting of a recombinant canine CD20 or a recombinant feline CD20 and
wherein the population of allogeneic tumor cell membrane extracts is generated by exposing a population of allogeneic tumor cells to a plurality of freeze/thaw cycles to disrupt the allogenic tumor cells, centrifuging the resulting cells, and collecting at least a portion of the resulting pellet for addition to the co-culture.
2. The method of claim 1 , further comprising isolating the feeder cell from whole peripheral blood by density centrifugation.
3. The method of claim 1 , further comprising adding an interleukin mixture comprising interleukin 21, interleukin 2, phytohemagglutinin, anti-CD3 antibody, or any combination thereof.
4. The method of claim 1 , further comprising adding interleukin 21 at least three times in a first week of the co-culture.
5. The method of claim 1 , further comprising co-administering interleukin 21 and interleukin 2 three times a week starting in a second week of the co-culture.
6. The method of claim 5 , further comprising adding the interleukin 2 to the co-culture at least three times a week in a second week of the co-culture, a third week of the co-culture, a fourth week of the co-culture, a fifth week of the co-culture, a sixth week of the co-culture, or any combination thereof.
7. The method of claim 1 , wherein the CD20 antigen specific cell is a T cell.
8. The method of claim 1 , wherein the recombinant thereof comprises at least 80% sequence identity to SEQ ID NO: 1 or SEQ ID NO: 3.
9. The method of claim 1 , wherein the feeder cell is an antigen presenting cell comprising a dendritic cell, a macrophage, or a B cell.
10. The method of claim 9 , wherein the antigen presenting cell is derived from a chronic lymphocytic leukemia cell line.
11. The method of claim 1 , wherein the feeder cell further expresses at least one human cell surface molecule comprising CD19, CD64, CD86, CD137L, membrane bound IL-15, or any combination thereof.
12. The method of claim 1 , wherein the feeder cell is heat killed or irradiated by a direct dose of gamma radiation.
13. The method of claim 1 , wherein the feeder cell is transfected with a nucleotide sequence encoding the recombinant CD20.
14. The method of claim 1 , wherein the feeder cell expresses a human cell surface molecule comprising CD19, CD64, CD86, CD137L, membrane bound IL-15, or any combination thereof.
15. The method of claim 1 , wherein exposing the population of allogenic tumor cells to a plurality of freeze/thaw cycles comprises exposing the population of allogeneic tumor cells to −120° C. for 5 minutes then thawing the population to 37° C.
16. The method of claim 1 , wherein the feeder cell is mixed with a human anti-CD3 antibody.
17. A method of treating a subject in need thereof comprising:
generating a CD20 antigen specific cell by contacting a cell with an allogeneic tumor cell membrane extract and a feeder cell presenting a recombinant canine CD20 or a recombinant feline CD20; and
administering the CD20 antigen specific cell to a subject in need thereof,
wherein the CD20 antigen specific cell is selected from the group consisting of a canine CD20 antigen specific cell and a feline CD20 antigen specific cell, and
wherein the allogeneic tumor cell membrane extract is generated by exposing a population of allogeneic tumor cells to a plurality of freeze/thaw cycles to disrupt the allogenic tumor cells, centrifuging the resulting cells, and contacting the cell with at least a portion of the resulting pellet.
18. The method of claim 17 , wherein the administering is an infusion via a peripheral vein catheter.
19. The method of claim 17 , wherein the administering comprises a first dose infused at a rate of from 5×10 5 cells/m 2 to 5×10 10 cells/m 2 .
20. The method of claim 19 , wherein the administering further comprises a second dose infused two weeks after the first dose, infused at a rate of from 5×10 5 to 5×10 10 cells/m 2 .
21. The method of claim 17 , further comprising conditioning the subject with a chemotherapy before the administering.
22. The method of claim 17 , wherein the subject is a canine.
23. The method of claim 17 , further comprising killing a cancer cell from a B cell lymphoma with the antigen specific cell.
24. The method of claim 17 , wherein the subject has a B cell lymphoma, a T cell lymphoma, an osteosarcoma, a hemangiosarcoma, multiple myeloma, or a plasma cell tumor.
25. The method of claim 17 , wherein the subject is a human.