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 pharmaceutical composition comprising (i) a pharmaceutically acceptable carrier, (ii) a medium, and (iii) modified NK-92 cells comprising 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.
2 . The pharmaceutical composition of claim 1 , wherein the mean doubling time of the cells is between 55 and 70 hours.
3 . The pharmaceutical composition of claim 1 , wherein the population of cells maintains the mean doubling time from 1, 2, 3, 4, 5, 10, 15, 20, or 25 days.
4 . The pharmaceutical composition of claim 1 , wherein the population of cells can be passaged every 1, 2, 3, or 4 days.
5 . The pharmaceutical composition of claim 1 , wherein the cells secrete IL-2 at a concentration of 10 to 60 pg/hour per million cells.
6 . The pharmaceutical composition of claim 1 , wherein the cells are irradiated cells.
7 . The pharmaceutical composition of claim 1 , wherein the cells have reduced downregulation of expression of CD16 compared to a control.
8 . The pharmaceutical composition of claim 1 , wherein the medium is human serum or an equivalent thereof.
9 . The pharmaceutical composition of claim 1 , wherein the medium comprises human serum albumin.
10 . The pharmaceutical composition of claim 1 , wherein the medium comprises human plasma.
11 . The pharmaceutical composition of claim 1 , wherein the medium comprises about 1% to about 15% human serum or human serum equivalent.
12 . The pharmaceutical composition of claim 1 , wherein the medium comprises about 1% to about 10% human serum or human serum equivalent.
13 . The pharmaceutical composition of claim 1 , wherein the medium comprises about 1% to about 5% human serum or human serum equivalent.
14 . The pharmaceutical composition of claim 1 , wherein the medium comprises about 2.5% human serum or human serum equivalent.
15 . The pharmaceutical composition of claim 8 , wherein the serum is human AB serum.
16 . The pharmaceutical composition of claim 1 , wherein the composition comprises an isotonic liquid solution that supports cell viability.
17 . The pharmaceutical composition of claim 1 , wherein the composition further comprises a buffering agent.
18 . A kit comprising the pharmaceutical composition of claim 1 and instructions for use.
19 . The kit of claim 18 , wherein the kit further comprises an antibody.