Immunitybio, Inc.

Nantkwest Inc.

Abhijit Dandapat

Hans G Klingemann

Laurent H Boissel

Himani Chinnapen

Patrick Soon-Shiong

Recombinant NK cells, and especially recombinant NK-92 cells express a chimeric antigen receptor (CAR) having an intracellular domain of FcεRIγ. Notably, CAR constructs with an intracellular domain of FcεRIγ had a substantially prolonged duration of expression and significantly extended cytotoxicity over time. The CAR may be expressed from RNA and DNA, preferably as a tricistronic construct that further encodes CD16 and a cytokine to confer autocrine growth support. Advantageously, such constructs also enable high levels of transfection and expression of the recombinant proteins and provide a convenient selection marker to facilitate rapid production of recombinant NK/NK-92 cells.

Fc-epsilon CAR

The present application is directed to methods and compositions that are useful for reducing the number of myeloid-derived suppressor cells (MDSC), tumor associated macrophages (TAM), or both in a subject. The methods include administering an antigen binding protein that binds to an antigen expressed by MDSC and/or TAM, or administering a modified T cell or NK-92 cell that expresses an antigen binding protein that binds to an antigen expressed by MDSC and/or TAM, or a combination of both, to a subject. For example, the antigen binding protein can bind to CD33 expressed by MDSC and/or TAM. The methods and compositions are useful for treating a disease associated with MDSC and/or TAM infiltration into a tissue or tumor.

Use of CD33CAR modified high affinity NK cells (t-haNK) to reduce myeloid-derived suppressor cells suppressor activity (or reduce negative impact on NK cell activity)

Recombinant NK cells, and especially recombinant NK-92 cells express a chimeric antigen receptor (CAR) having an intracellular domain of Fc&#x3b5;RI&#x3b3;. Notably, CAR constructs with an intracellular domain of Fc&#x3b5;RI&#x3b3; had a substantially prolonged duration of expression and significantly extended cytotoxicity over time. The CAR may be expressed from RNA and DNA, preferably as a tricistronic construct that further encodes CD16 and a cytokine to confer autocrine growth support. Advantageously, such constructs also enable high levels of transfection and expression of the recombinant proteins and provide a convenient selection marker to facilitate rapid production of recombinant NK/NK-92 cells.

Fc-epsilon car

Provided herein are compositions of NK-92&#x2122; cells that express a combination of PD-L1 CAR, CD16 and IL2, and the method of using these cells to reduce tumor cells and cells in tumor microenvironment (e.g., MDSCs or TAMs) and treat cancer.

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San Diego, CA, United States of America

Abhijit Dandapat