ANTIBODY PRE-LOADED CD16+NK-92 CELLS AS AN EFFECTIVE THERAPEUTIC PRODUCT FOR TUMOR LYSIS
Provided herein are pharmaceutical compositions, comprising a pharmaceutically acceptable carrier and therapeutically effective amounts of high affinity Natural Killer (haNK) cells and a therapeutic antibody in the form of a combined preparation. Also provided herein are methods for treating cancer by using the pharmaceutical composition comprising the haNK cells and the therapeutic antibody.
1 . A pharmaceutical composition comprising a pharmaceutically acceptable carrier and therapeutically effective amounts of high affinity Natural Killer (haNK) cells and a therapeutic antibody in the form of a combined preparation.
2 . The pharmaceutical composition of claim 1 , wherein the haNK cell is a NK-92 cell line derivative.
3 . The pharmaceutical composition of claim 1 wherein the haNK cell further expresses recombinant IL2.
4 . The pharmaceutical composition of claim 1 wherein the haNK cell is genetically engineered to have a reduced expression of at least one inhibitory receptor.
5 . The pharmaceutical composition of claim 1 wherein the haNK cell is irradiated before administration at a radiation dose of at least 500 cGy.
6 . The pharmaceutical composition of claim 1 wherein the antibody is an anti-CD20 antibody.
7 . The pharmaceutical composition of claim 6 , wherein the anti-CD20 antibody is Rituximab.
8 . The pharmaceutical composition of claim 1 wherein the antibody is selected from the group consisting of Atezolizumab, Ofatumumab, Ipilimumab, Ramucirumab, Olaratumab, Elotuzumab, Necitumumab, Daratumumab, Dinutuximab, Avelumab, Durvalumab, Trastuzumab, Alemtuzumab, Bevacizumab, Pertuzumab, Obinutuzumab, Rituximab, and Cetuximab.
9 . The pharmaceutical composition of claim 1 further comprising a cryopreservation medium.
10 . The pharmaceutical composition of claim 9 , wherein the cryopreservation medium is CryoStor CS10.
11 . The pharmaceutical composition of claim 9 , wherein the cryopreservation medium increases or stabilizes antibody binding to the haNK cells.
12 . A method of making a composition according to claim 1 , comprising:
mixing haNK cells with a therapeutic antibody to produce a combined preparation;
freezing the combined preparation; and
thawing the combined preparation.
13 . The method of claim 12 , wherein the haNK cells are in a medium comprising about 5% albumin.
14 . The method of claim 12 , wherein the haNK cells and therapeutic antibody mixture is mixed with an equivalent volume of a cryopreservation medium.
15 . The method of claim 12 , wherein the combined preparation is frozen to a temperature less than −80° C.
16 . The method of claim 12 , wherein the combined preparation is frozen to a temperature less than −120° C.
17 . The method of claim 12 , wherein the frozen combined preparation is irradiated with a fixed dose of X-ray irradiation to impair a proliferative ability of the haNK cells.
18 . The method of claim 12 , wherein, after the thawing step, the combined preparation is incubated on ice or room temperature for at least 10 minutes.
19 - 31 . (canceled)
32 . A kit comprising a pharmaceutical composition, wherein the pharmaceutical composition comprises haNK cells, a therapeutic antibody, and a cryopreservation medium or a cell growth medium.
33 . The kit of claim 32 , wherein the composition is packaged in bags or vials suitable for storage in less than −85° C.
34 . (canceled)