T cell receptors recognizing HLA-CW8 restricted mutated KRAS
AssigneeThe United States of America, as represented by the Secretary, Department of Health and Human Services
InventorsEric Tran, Yong-Chen Lu, Steven A. Rosenberg
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Abstract
Disclosed is an isolated or purified T cell receptor (TCR) having antigenic specificity for mutated Kirsten rat sarcoma viral oncogene homolog (KRAS) presented in the context of an HLA-Cw*0802 molecule. Related polypeptides and proteins, as well as related nucleic acids, recombinant expression vectors, host cells, populations of cells, and pharmaceutical compositions are also provided. Also disclosed are methods of detecting the presence of cancer in a mammal and methods of treating or preventing cancer in a mammal.
Claims20
A method of producing an engineered population of human cells, the method comprising:
- introducing a recombinant expression vector to an isolated population of human cells, wherein the recombinant expression vector comprises a nucleotide sequence encoding a T cell receptor (TCR), wherein the TCR comprises:
- (a) an α chain complementarity determining region (CDR) 1 comprising the amino acid sequence of SEQ ID NO:
- 3, an α chain CDR2 comprising the amino acid sequence of SEQ ID NO:
- 4, and an α chain CDR3 comprising the amino acid sequence of SEQ ID NO:
- 5;
- and
- (b) a β chain CDR1 comprising the amino acid sequence of SEQ ID NO:
- 6, a β chain CDR2 comprising the amino acid sequence of SEQ ID NO:
- 7, and a β chain CDR3 comprising the amino acid sequence of SEQ ID NO:
- 8.
A method for inducing an immune response against a cancer in a mammal, the method comprising administering to the mammal a population of host cells in an amount effective to induce an immune response against the cancer in the mammal, wherein the cancer expresses human leukocyte antigen (HLA)-Cw8 and Kirsten rat sarcoma viral oncogene homolog (KRAS) G12D and wherein the host cells of the population comprise a recombinant expression vector comprising a nucleic acid comprising a nucleotide sequence encoding a T-cell receptor (TCR) having antigenic specificity for KRAS G12D presented by an HLA-Cw8 molecule, and wherein the TCR comprises:
- (I) an α chain complementarity determining region (CDR) 1 comprising the amino acid sequence of SEQ ID NO:
- 3, an α chain CDR2 comprising the amino acid sequence of SEQ ID NO:
- 4, and an α chain CDR3 comprising the amino acid sequence of SEQ ID NO:
- 5;
- and
- (II) a β chain CDR1 comprising the amino acid sequence of SEQ ID NO:
- 6, a β chain CDR2 comprising the amino acid sequence of SEQ ID NO:
- 7, and a β chain CDR3 comprising the amino acid sequence of SEQ ID NO:
- 8.
An isolated or purified nucleic acid comprising a nucleotide sequence encoding a polypeptide comprising a functional portion of a T-cell receptor (TCR) having antigenic specificity for KRAS G12D presented by an HLA-Cw8 molecule, wherein the functional portion comprises the amino acid sequences of SEQ ID NOs:
- 3-8.
Dependencies are inferred from the claim text.