HLA class II-restricted DRB T cell receptors against RAS with G12V mutation
AssigneeThe United States of America, as represented by the Secretary, Department of Health and Human Services
InventorsNoam Levin, Frank J. Lowery, III, Maria R. Parkhurst, Steven A. Rosenberg
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Abstract
Disclosed is an isolated or purified T cell receptor (TCR), wherein the TCR has antigenic specificity for a mutated human RAS amino acid sequence with a substitution of glycine at position 12 with valine. The TCRs may recognize G12V RAS presented by an HLA-DR heterodimer. 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.
Claims41
An isolated or purified T-cell receptor (TCR) comprising the amino acid sequences of
- all of SEQ ID NOs:
- 1-6,
- wherein the TCR has antigenic specificity for a mutated human RAS amino acid sequence with a substitution of glycine at position 12 with valine,
- wherein the mutated human RAS amino acid sequence is a mutated human Kirsten rat sarcoma viral oncogene homolog (KRAS), a mutated human Harvey rat sarcoma viral oncogene homolog (HRAS), or a mutated human Neuroblastoma rat sarcoma viral oncogene homolog (NRAS) amino acid sequence, and
- wherein position 12 is defined by reference to the wild-type human KRAS, wild-type human HRAS, or wild-type human NRAS protein, respectively.
An isolated or purified protein comprising a first polypeptide chain comprising the amino acid sequences of SEQ ID NOs:
- 1-3 and a second polypeptide chain comprising the amino acid sequences of SEQ ID NOs:
- 4-6.
An isolated or purified nucleic acid comprising, from 5′ to 3′, a first nucleotide sequence and a second nucleotide sequence, wherein the first and second nucleotide sequence, respectively, encode the amino sequences of SEQ ID NOs:
- 7 and 8;
- 8 and 7;
- 9 and 10;
- 10 and 9;
- 25 and 26;
- 26 and 25;
- 27 and 28;
- 28 and 27;
- 29 and 30;
- 30 and 29;
- 31 and 32;
- or 32 and 31.
Dependencies are inferred from the claim text.