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US 2026/0216333 A1Published application
T cell receptors targeting the highly prevalent kras g12v mutation on hla-a*03:01 in lung cancer
AssigneeBoard of Regents, The University of Texas System
InventorsAlexandre REUBEN, Minying ZHANG, John Victor HEYMACH, Gregory A. LIZEE, Peixin JIANG
Life of this patent
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Abstract
The present disclosure is directed to recombinant T-cell Receptors (TCRs) that binds Kirsten Rat Sarcoma Viral Oncogene Homolog (KRAS) protein comprising a G12V mutation presented on a human leucocyte antigen-A (HLA-A)*03:01, polynucleotides encoding such TCRs, engineered T-cells comprising such TCRs, and methods of using the same.
Claims59
A recombinant T-cell Receptor (TCR) comprising:
- (a) a TCR alpha chain comprising (i) a variable TCR alpha chain complementary determining region 1 (CDR1α) of SEQ ID NO:
- 15, 16, 31, 32, 63, or 64, (ii) a CDR2α of SEQ ID NO:
- 15, 16, 31, 32, 63, or 64, and (iii) a CDR3α of SEQ ID NO:
- 15, 16, 31, 32, 63, or 64;
- and (b) a TCR beta chain comprising (i) a variable TCR beta chain complementary determining region 1 (CDR1β) of SEQ ID NO:
- 17, 18, 35, 36, 67, or 68, (ii) a CDR2β of SEQ ID NO:
- 17, 18, 35, 36, 67, or 68, and (iii) a CDR3β of SEQ ID NO:
- 17, 18, 35, 36, 67, or 68, wherein the recombinant TCR binds an epitope of a Kirsten Rat Sarcoma Viral Oncogene Homolog (KRAS) protein comprising a G12V mutation presented on a human leucocyte antigen-A (HLA-A)*03:01, wherein the epitope comprises the amino acid sequence of VVGAVGVGK (SEQ ID NO:
- 1).
6 more elements
A modified T cell comprising a T cell receptor (TCR) comprising:
- (a) a TCR alpha chain comprising (i) a variable TCR alpha chain complementary determining region 1 (CDR1α) of SEQ ID NO:
- 15, 16, 31, 32, 63, or 64, (ii) a CDR2α of SEQ ID NO:
- 15, 16, 31, 32, 63, or 64, and (iii) a CDR3α of SEQ ID NO:
- 15, 16, 31, 32, 63, or 64;
- and (b) a TCR beta chain comprising (i) a variable TCR beta chain complementary determining region 1 (CDR1β) of SEQ ID NO:
- 17, 18, 35, 36, 67, or 68, (ii) a CDR2β of SEQ ID NO:
- 17, 18, 35, 36, 67, or 87, and (iii) a CDR3β of SEQ ID NO:
- 17, 18, 35, 36, 67, or 68, wherein the TCR binds an epitope of a Kirsten Rat Sarcoma Viral Oncogene Homolog (KRAS) protein comprising a G12V mutation presented on a human leucocyte antigen-A (HLA-A)*03:01, wherein the epitope comprises the amino acid sequence of VVGAVGVGK (SEQ ID NO:
- 1).
6 more elements
A bi-specific T-cell engager (BiTE) comprising a T cell receptor (TCR) comprising:
- (a) a TCR alpha chain comprising (i) a variable TCR alpha chain complementary determining region 1 (CDR1α) of SEQ ID NO:
- 15, 16, 31, 32, 63, or 64, (ii) a CDR2α of SEQ ID NO:
- 15, 16, 31, 32, 63, or 64, and (iii) a CDR3α of SEQ ID NO:
- 15, 16, 31, 32, 63, or 64;
- and (b) a TCR beta chain comprising (i) a variable TCR beta chain complementary determining region 1 (CDR1β) of SEQ ID NO:
- 17, 18, 35, 36, 67, or 68, (ii) a CDR2B of SEQ ID NO:
- 17, 18, 35, 36, 67, or 68, and (iii) a CDR3β of SEQ ID NO:
- 17, 18, 35, 36, 67, or 68, wherein the TCR binds an epitope of a Kirsten Rat Sarcoma Viral Oncogene Homolog (KRAS) protein comprising a G12V mutation presented on a human leucocyte antigen-A (HLA-A)*03:01, wherein the epitope comprises the amino acid sequence of VVGAVGVGK (SEQ ID NO:
- 1).
6 more elements
Dependencies are inferred from the claim text.