Macrophage CAR (MOTO-CAR) in immunotherapy
Modified macrophage immune cells are provided for treatment of cancer and other diseases.
1. A method for administering cells to a tumor in a subject, the method comprising:
administering to the subject human monocyte cells;
wherein the monocyte cells comprise a gene encoding a chimeric antigen receptor (CAR);
wherein the CAR comprises a fusion of an antigen binding antibody fragment and a TLR-4 cytoplasmic signaling domain, the cytoplasmic signaling domain polarizing the cells to M1 phenotype macrophages upon binding of the antibody fragment to its antigen.
2. The method according to claim 1 , wherein the antibody fragment is a single chain variable fragment (scFv).
3. The method according to claim 1 , wherein the antigen is HGPRT.
4. The method according to claim 2 , wherein the scFv is derived from a monoclonal antibody specific for an antigen expressed by cells of a cancer.
5. The method according to claim 1 , wherein the antigen is present on cells of a cancer.
6. The method according to claim 4 , wherein the monoclonal antibody is a human or mouse monoclonal antibody.
7. The method according to claim 1 , wherein the macrophages are stimulated by a co-stimulatory molecule.
8. The method according to claim 7 , wherein the co-stimulatory molecule is MD2 or CD14.
9. A method for administering cells to a tumor in a subject, the method comprising:
administering to the subject human monocyte cells;
wherein the monocyte cells comprise a gene encoding a chimeric antigen receptor (CAR);
wherein the gene encoding the CAR comprises a macrophage specific promoter;
wherein the CAR comprises a fusion of an antigen binding antibody fragment and a TLR-4 cytoplasmic signaling domain, the cytoplasmic signaling domain polarizing the cells to M1 phenotype macrophages upon binding of the antibody fragment to its antigen; and
wherein the antigen is TK1.
10. The method according to claim 1 , wherein the antigen is a salvage pathway enzyme.
11. The method according to claim 10 , wherein the salvage pathway enzymes is selected from the group consisting of TK1, HGPRT, DCK, and APRT.
12. The method according to claim 1 , wherein the gene encoding the CAR comprises a macrophage specific promoter.