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)
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.
1. A method for reducing the number of myeloid-derived suppressor cells (MDSC), tumor associated macrophages (TAM), or both, in a subject in need thereof, the method comprising:
administering to the subject, intravenously or by injection, a therapeutically effective amount of a genetically modified cell comprising a chimeric antigen receptor (CAR) that specifically binds CD33, wherein the CAR comprises an amino acid sequence having at least 95% sequence identity to SEQ ID NO: 16, and
wherein the genetically modified cell is a T cell or NK-92 cell.
2. The method of claim 1 , wherein about 1×10 8 to about 1×10 11 modified cells per m 2 of body surface area of the subject are administered to the subject.
3. A composition comprising a genetically modified cell comprising a chimeric antigen receptor (CAR) that specifically binds CD33, wherein the CAR comprises an amino acid sequence having at least 95% sequence identity to SEQ ID NO: 16, and wherein the genetically modified cell is a T cell or NK-92 cell.