An isolated nucleic acid that contains a nucleotide sequence that encodes the polypeptide of SEQ ID NO: 3. The polypeptide of SEQ ID NO: 3 specifically binds to stage-specific embryonic antigen 4 (SSEA4). Also disclosed is a recombinant cell comprising the isolated nucleic acid described above, a viral vector containing the above isolated nucleic acid, and an isolated polypeptide including the sequence of SEQ ID NO: 3. Provided as well is a chimeric antigen receptor (CAR) that includes a single chain Fv having the sequence of SEQ ID NO: 3 and specifically binding to SSEA4. Moreover, a method is disclosed for treating a tumor by transducing in vitro the T cells of a subject having a tumor expressing SSEA4 with a vector that encodes the CAR, expanding the transduced T cells, and infusing the expanded transduced T cells into the subject, whereby an anti-tumor T cell response is raised.

The present invention relates to Chimeric Antigen Receptors (CAR) that are recombinant chimeric proteins able to redirect immune cell specificity and reactivity toward selected membrane antigens, and more particularly in which extracellular ligand binding is a scFV derived from a 5T4 monoclonal antibody, conferring specific immunity against 5T4 positive cells. The engineered immune cells endowed with such CARs are particularly suited for treating lymphomas and leukemia, and for solid tumors such as colon, stomach, and ovarian tumors.

A method for treating a tumor includes administering (i) a vaccine that contains stage-specific embryonic antigen 4 conjugated to a carrier, (ii) an antibody that binds specifically to SSEA-4, and (iii) immune cells expressing a chimeric antigen receptor that specifically binds to SSEA-4. The tumor, which expresses SSEA-4, can be a breast, colon, gastrointestinal, kidney, lung, liver, ovarian, pancreatic, rectal, stomach, testicular, thymic, cervical, prostate, bladder, skin, nasopharyngeal, esophageal, oral, head and neck, bone, cartilage, muscle, lymph node, bone marrow, or brain tumor.

A method for treating a tumor in a subject by administering at least three of the following treatment modalities: (i) an antibody, (ii) T cells bearing a first chimeric antigen receptor (CAR), (iii) NK cells bearing a second CAR, and (iv) NKT cells bearing a third CAR. The antibody binds specifically to stage-specific embryonic antigen 4 and each CAR contains a scFv that also binds specifically to SSEA4.

A chimeric antigen receptor containing (i) a single chain Fv that specifically binds to stage-specific embryonic antigen 4 and (ii) an endodomain from CD3 or FcRI. Also provided is a nucleic acid encoding the chimeric antigen receptor and an expression vector that contains the nucleic acid operably linked to a promoter that is active in T cells. Furthermore, two similar methods for treating a tumor are disclosed. The first method includes (i) obtaining T cells from a subject, (ii) transducing the T cells in vitro with an expression vector encoding a chimeric antigen receptor that contains an scFv specifically recognizing stage-specific embryonic antigen 4, (iii) expanding the transduced T cells in vitro, and (iv) infusing the expanded transduced T cells into the subject. The second method includes, in place of step (ii) above, transducing the T cells in vitro with an expression vector encoding a chimeric antigen receptor that is specific for a tumor antigen other than stage-specific embryonic antigen 4, and further requires a step of administering an antibody against stage-specific embryonic antigen 4.

Two methods for treating a tumor are disclosed. The first method includes (i) obtaining NK cells or NKT cells from a subject, (ii) transducing the NK cells or NKT cells in vitro with an expression vector encoding a chimeric antigen receptor that contains an scFv specifically recognizing stage-specific embryonic antigen 4, (iii) expanding the transduced NK cells or NKT cells in vitro, and (iv) infusing the expanded transduced NK cells or NKT cells into the subject. The second method includes, in place of step (ii) above, transducing the NK cells or NKT cells in vitro with an expression vector encoding a chimeric antigen receptor that is specific for a tumor antigen other than stage-specific embryonic antigen 4, and further requires a step of administering an antibody against stage-specific embryonic antigen 4.