The present invention is directed to a chimeric antigen receptor (CAR) fusion protein comprising from N-terminus to C-terminus: (i) a single-chain variable fragment (scFv) comprising V.sub.H and V.sub.L, wherein scFv binds to human PLAP (placental alkaline phosphatase), (ii) a transmembrane domain, (iii) a co-stimulatory domain of CD28, OX-40, GITR, or 4-1BB, and (iv) CD3 an activating domain. The present invention is also directed to T cells, natural killer (NK) cells, or macrophages, modified to express the CAR of the present invention. The present invention is further directed to a method for treating PLAP-positive cancer cells by administering PLAP-CAR-T cells, PLAP-CAR-NK cells, or PLAP-CAR-macrophages to the patients.

The present invention is directed to a chimeric antigen receptor (CAR) fusion protein comprising from N-terminus to C-terminus: (i) a single-chain variable fragment (scFv) comprising V.sub.H and V.sub.L, wherein scFv binds to human PLAP (placental alkaline phosphatase), (ii) a transmembrane domain, (iii) a co-stimulatory domain of CD28, OX-40, GITR, or 4-1BB, and (iv) CD3 an activating domain. The present invention is also directed to T cells, natural killer (NK) cells, or macrophages, modified to express the CAR of the present invention. The present invention is further directed to a method for treating PLAP-positive cancer cells by administering PLAP-CAR-T cells, PLAP-CAR-NK cells, or PLAP-CAR-macrophages to the patients.

Disclosed herein are methods of administering an agent targeting a lineage-specific cell-surface antigen and a population of hematopoietic cells that are deficient in the lineage-specific cell-surface antigen for immunotherapy of hematological malignancies.

Disclosed herein are methods of administering an agent targeting a lineage-specific cell-surface antigen and a population of hematopoietic cells that are deficient in the lineage-specific cell-surface antigen for immunotherapy of hematological malignancies.

Disclosed herein are methods of administering an agent targeting a lineage-specific cell-surface antigen and a population of hematopoietic cells that are deficient in the lineage-specific cell-surface antigen for immunotherapy of hematological malignancies.

Provided herein are recombinant nucleic acids encoding chimeric priming receptors that bind ALPG/P, chimeric antigen receptors that bind MSLN, and shRNA that target FAS, PTPN2, and/or TOX. Also provided are systems of chimeric priming receptors that bind ALPG/P, chimeric antigen receptors that bind MSLN, and shRNA that target FAS, PTPN2, and/or TOX, cells expressing such proteins and shRNA, and methods of use thereof.