T cell immunotherapy specific for WT-1
AssigneeFred Hutchinson Cancer Research Center
InventorsThomas M. Schmitt, Philip D. Greenberg, Hieu Nguyen
Life of this patent
Estimating the term…
Abstract
The present disclosure provides high affinity and enhanced affinity T cell receptors specific for human Wilms tumor protein 1 (WT-1) epitopes for use in treating diseases or disorders, such as cancer cells that overexpress WT-1.
Claims47
An isolated polynucleotide encoding a binding protein, comprising a polynucleotide encoding a human TCR α-chain variable (Vα) domain that contains the complementarity determining region 3 (CDR3) amino acid sequence of SEQ ID NO.:25 or 26, the CDR1 amino acid sequence of SEQ ID NO:
- 23, and the CDR2 amino acid sequence of SEQ ID NO:
- 24, wherein the polynucleotide encoding the Vα domain is at least 80% identical to the nucleotide sequence of SEQ ID NO 78, 128 or 80, provided that the Vα domain comprises the CDR3 of SEQ ID NO:25 or 26, the CDR1 of SEQ ID NO:23 and the CDR2 of SEQ ID NO:24;
- and a polynucleotide encoding a human TCR β-chain variable (Vβ) domain that contains the CDR3 amino acid sequence of SEQ ID NO.:29, the CDR1 amino acid sequence of SEQ ID NO:27, and the CDR2 amino acid sequence of SEQ ID NO:28, wherein the polynucleotide encoding the Vβ domain is at least 80% identical to the nucleotide sequence of SEQ ID NO. 89, provided that the Vβ domain comprises the CDR3 of SEQ ID NO:29, the CDR1 of SEQ ID NO:27 and the CDR2 of SEQ ID NO:28;
- and wherein the encoded binding protein specifically binds to a RMFPNAPYL (SEQ ID NO.:16):human leukocyte antigen-A*201 (HLA-A*201) complex.
An isolated polynucleotide encoding a binding protein, comprising a polynucleotide encoding a human TCR α chain variable (Vα) domain, wherein the polynucleotide encoding the Vα domain comprises the nucleotide sequence of SEQ ID NO.:128;
- and a polynucleotide encoding a human TCR β chain variable (Vβ) domain, wherein the polynucleotide encoding the Vβ domain comprises the nucleotide sequence of SEQ ID NO.:89.
An isolated polynucleotide comprising the nucleotide sequence of SEQ ID NO:96.
An isolated polynucleotide comprising the nucleotide sequence of SEQ ID NO:97.
Dependencies are inferred from the claim text.