Compositions comprising T cell receptors and methods of use thereof
View Patent ↗Nucleic acids encoding antitumor TCRs recognizing MART-1, NY-ESO-1, and melanoma gp100 peptides; vectors and cells comprising the same; and methods of using the foregoing.
1. An isolated nucleic acid molecule encoding an amino acid sequence selected from the group consisting of SEQ ID NO: 2 and SEQ ID NO: 4, and wherein said nucleic acid molecule encodes a chain of a T cell receptor (TCR) which binds a tumor antigen in the context of a major histocompatibility complex (MHC).
2. The isolated nucleic acid molecule of claim 1 wherein the nucleic acid molecule encodes the alpha (α) chain of a TCR that recognizes a tumor antigen.
3. The isolated nucleic acid molecule of claim 1 , wherein the nucleic acid molecule encodes the beta (β) chain of a TCR that recognizes a tumor antigen.
4. The isolated nucleic acid molecule of claim 1 , wherein the nucleic acid molecule comprises a sequence consisting essentially of SEQ ID NO: 1 or SEQ ID NO: 3.
5. A vector comprising the isolated nucleic acid molecule of claim 1 .
6. The vector of claim 5 , wherein the vector is a viral vector.
7. The vector of claim 6 , wherein the viral vector is a retroviral vector.
8. A composition comprising the isolated nucleic acid molecule of claim 1 , wherein the nucleic acid molecule optionally is inserted into a vector, and a pharmaceutically acceptable carrier.
9. An isolated nucleic acid molecule encoding a polypeptide comprising the variable and hypervariable portions of SEQ ID NO: 2 and SEQ ID NO: 4, wherein the polypeptide recognizes a MART-1 peptide in the context of an MHC.
10. A method of making a tumor-reactive T lymphocyte, comprising transducing a T lymphocyte with a nucleic acid molecule encoding SEQ ID NO: 2 and SEQ ID NO: 4, wherein the nucleic acid molecule is inserted into a vector.
11. The nucleic acid molecule of claim 1 , wherein the tumor antigen is MART-1.