Cyclin A1 specific T cell receptors and uses thereof
AssigneeFred Hutchinson Cancer Center
InventorsRachel Perret, Philip D. Greenberg
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Abstract
The present disclosure provides binding proteins, including TCRs, that specifically bind human cyclin A1 (CCNA1), host cells expressing such antigen specific binding proteins, nucleic acids encoding the same, and compositions for use in treating diseases or disorders in which cells overexpress CCNA1, such as in cancer.
Claims21
An isolated T cell receptor (TCR) comprising a TCR α chain and a TCR β chain, wherein the TCR α chain comprises a TCR α chain variable (Vα) domain and a TCR α chain constant (Cα) domain and the TCR β chain comprises a TCR β chain variable (Vβ) domain and a TCR β chain constant (Cβ) domain, wherein:
- the Vα domain comprises the amino acid sequence of SEQ ID NO:128 and the Vβ domain comprises the amino acid sequence of SEQ ID NO:130;
- the Cα domain comprises a cysteine substitution, the Cβ domain comprises a cysteine substitution, and the cysteine substitution in the Cα domain and the cysteine substitution in the Cβ domain create a disulfide bond between the Cα domain and the Cβ domain which is not present in a TCR comprising the native Cα domain and the native Cβ domain;
- and
- the TCR is capable of specifically binding to a human cyclin A1 (CCNA1) peptide FLDRFLSCM (SEQ ID NO:1):human leukocyte antigen-A*02:01 (HLA-A*02:01) complex.
An isolated CD3+ T cell comprising a heterologous polynucleotide encoding a T cell receptor (TCR) comprising a TCR α chain and a TCR β chain, wherein the TCR α chain comprises a TCR α chain variable (Vα) domain and a TCR α chain constant (Cα) domain and the TCR β chain comprises a TCR β chain variable (Vβ) domain and a TCR β chain constant (Cβ) domain, wherein:
- the Vα domain comprises the amino acid sequence of SEQ ID NO:128 and the Vβ domain comprises the amino acid sequence of SEQ ID NO:130;
- and
- the TCR is capable of specifically binding to a human cyclin A1 (CCNA1) peptide FLDRFLSCM (SEQ ID NO:1):human leukocyte antigen-A*02:01 (HLA-A*02:01) complex.
An isolated polynucleotide encoding a T cell receptor (TCR) comprising a TCR α chain and a TCR β chain, wherein the TCR α chain comprises a TCR α chain variable (Vα) domain and a TCR α chain constant (Cα) domain and the TCR β chain comprises a TCR β chain variable (Vβ) domain and a TCR β chain constant (Cβ) domain, wherein:
- the Vα domain comprises the amino acid sequence of SEQ ID NO:130 the domain comprises the amino acid sequence of SEO ID NO:130;
- the TCR is capable of specifically binding to a human cyclin A1 (CCNA1) peptide FLDRFLSCM (SEQ ID NO:1):human leukocyte antigen-A*02:01 (LAA*02:01) complex;
- the polynucleotide comprises a heterologous expression control sequence disposed upstream of a sequence encoding the TCR β chain and a sequence encoding the TCR α chain, and/or the polynucleotide comprises a sequence encoding a self-cleaving peptide, wherein the sequence encoding a self-cleaving peptide is disposed between the TCR β chain-encoding sequence and the TCR α chain-encoding sequence.
An isolated polynucleotide encoding the amino acid sequence set forth in SEQ ID NO:178.
An isolated viral vector encoding a T cell receptor (TCR), wherein the TCR comprises a TCR α chain and a TCR β chain, wherein the TCR α chain comprises a TCR α chain variable (Vα) domain and a TCR α chain constant (Cα) domain and the TCR β chain comprises a TCR β chain variable (Vβ) domain and a TCR β chain constant (Cβ) domain, wherein:
- the Vα domain comprises the amino acid sequence of SEQ ID NO:128 and the Vβ domain comprises the amino acid sequence of SEQ ID NO:130;
- and
- the TCR is capable of specifically binding to a human cyclin A1 (CCNA1) peptide FLDRFLSCM (SEQ ID NO:1):human leukocyte antigen-A*02:01 (HLA-A*02:01) complex.
Dependencies are inferred from the claim text.