Hla class ii-restricted t cell receptors against ras with g12r mutation
AssigneeThe United States of America, as represented by the Secretary, Department of Health and Human Services
InventorsRami Yoseph, Maria R. Parkhurst, Anna Pasetto, Steven A. Rosenberg
Life of this patent
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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 arginine. 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.
Claims44
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 arginine,
- 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.
A TCR, comprising the amino acid sequences of:
- (a) all of SEQ ID NOs:
- 1-3,
- (b) all of SEQ ID NOs:
- 4-6,
- (c) all of SEQ ID NOs:
- 7-9,
- (d) all of SEQ ID NOs:
- 10-12,
- (e) all of SEQ ID NOs:
- 1-6, or
- (f) all of SEQ ID NOs:
- 7-12.
An isolated or purified nucleic acid comprising, from 5′ to 3′, a first nucleic acid sequence and a second nucleotide sequence, wherein the first and second nucleotide sequence, respectively, encode the amino sequences at least 95% identical to the amino acid sequences of SEQ ID NOs:
- 13 and 14;
- 14 and 13;
- 15 and 16;
- 16 and 15;
- 30 and 31;
- 31 and 30;
- 32 and 33;
- 33 and 32;
- 34 and 35;
- 35 and 34;
- 36 and 37;
- 37 and 36;
- 41 and 42;
- 42 and 41;
- 43 and 44;
- 44 and 43;
- 45 and 46;
- 46 and 45;
- 47 and 48;
- 48 and 47;
- 49 and 50;
- 50 and 49;
- 51 and 52;
- or 52 and 51.
37-43. (canceled)
Dependencies are inferred from the claim text.