Modified NK-92 haNK003 cells for the clinic
Provided herein are populations of modified NK-92 cells, compositions and kits comprising the cells, and methods of making and using the populations of cells.
1. A method of treating cancer in a subject in need thereof, the method comprising:
(a) administering to the subject a population of modified NK-92 cells, wherein the modified NK-92 cells comprise a polypeptide with at least 90% identity to SEQ ID NO:4 (CD16) and a polypeptide with at least 90% identity to SEQ ID NO:6 (IL-2) and wherein the cells comprise SEQ ID NO:1 on chromosome 17, wherein greater than 90% of the cells in the population of cells express CD56, CD16, CD54, and NKp30 and wherein fewer than 5% of the cells in the population of cells express CD3; and
(b) administering to the subject an antibody.
2. The method of claim 1 , wherein the cells comprise a polypeptide with at least 98% identity to SEQ ID NO:4 and a polypeptide with at least 98% identity to SEQ ID NO:6.
3. The method of claim 1 , wherein the mean doubling time of the cells is between 55 and 70 hours.
4. The method of claim 3 , wherein the population of cells maintains the mean doubling time from 10 days.
5. The method of claim 4 , further comprising passaging the population of cells every 1, 2, 3, or 4 days before administration.
6. The method of claim 5 , wherein the cells secrete IL-2 at a concentration of 10 to 60 pg/hour per million cells.
7. The method of claim 1 , wherein the cells are irradiated cells.
8. The method of claim 7 , wherein the cells comprise a polypeptide according to SEQ ID NO:4 and a polypeptide according to SEQ ID NO:6.
9. The method of claim 3 , wherein the antibody is a monoclonal antibody.
10. The method of claim 9 , wherein the cancer is a cancer of the brain, breast, cervix, colon, head & neck, liver, kidney, lung, non-small cell lung, or stomach.
11. The method of claim 10 , wherein the population of cells and the antibody are administered separately.
12. The method of claim 10 , wherein the population of cells and the antibody are administered in the same formulation.
13. The method of claim 1 , wherein the population of cells and the antibody are administered in separate formulations.
14. The method of claim 10 , wherein the antibody is selected from the group consisting of alemtuzumab, bevacizumab, ibritumomab tiuxetan, ofatumumab, rituximab, and trastuzumab.
15. The method of claim 14 , wherein the population of cells and the antibody are administered on the same day.
16. The method of claim 15 , wherein between 1×10 9 and 1×10 10 cells are administered per dose.
17. The method of claim 16 , wherein multiple doses of cells are administered to the subject.
18. The method of claim 1 , wherein the cells are capable of secreting IL-2 at a concentration of 10 to 40 pg/hour per million cells.