Chimeric antigen receptors that bind to SSEA4 and uses thereof
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.
1. An isolated nucleic acid, comprising a nucleotide sequence that encodes the polypeptide as set forth in SEQ ID NO: 3.
2. The isolated nucleic acid of claim 1 , wherein the nucleotide sequence is SEQ ID NO: 1.
3. An isolated recombinant cell comprising the isolated nucleic acid of claim 2 , wherein the isolated recombinant cell expresses the polypeptide of SEQ ID NO: 2.
4. The isolated recombinant cell of claim 3 , wherein the cell is a T cell.
5. A viral vector comprising the isolated nucleic acid of claim 1 .
6. The viral vector of claim 5 , wherein the nucleotide sequence is SEQ ID NO: 1.
7. A method for treating a tumor in a subject, the method comprising:
(i) obtaining T cells from a subject having a breast tumor;
(ii) transducing the T cells in vitro with a vector comprising a nucleic acid encoding a chimeric antigen receptor (CAR) comprising the amino acid sequence as set forth in SEQ ID NO: 3 that specifically recognizes stage-specific embryonic antigen 4 (SSEA4), whereby the transduced T cells express the CAR;
(iii) expanding the transduced T cells expressing the CAR in vitro; and
(iv) infusing the expanded transduced T cells expressing the CAR into the subject having the breast tumor, thereby eliciting an anti-tumor T cell response, wherein cells in the breast tumor express SSEA4.
8. The method of claim 7 , wherein the CAR has the amino acid sequence as set forth in SEQ ID NO: 4.
9. The method of claim 8 , wherein the vector is a lentivirus, a gamma retrovirus, or an adeno-associated virus.
10. The viral vector of claim 5 , wherein the viral vector is a lentiviral vector, a gamma-retroviral vector, or an adeno-associated viral vector.