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US 11,878,062 B2Granted
Multimeric T-cell modulatory polypeptides and methods of use thereof
AssigneeCue Biopharma, Inc.
InventorsSaso Cemerski, Ronald D. Seidel, III, Rodolfo J. Chaparro, John F. Ross
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Abstract
The present disclosure provides T-cell modulatory multimeric polypeptides that comprise an immunomodulatory polypeptide and that comprise an epitope-presenting Wilms tumor peptide. A T-cell modulatory multimeric polypeptide is useful for modulating the activity of a T cell, and for modulating an immune response in an individual.
Claims4
A homodimer comprising two heterodimers, wherein each heterodimer comprises:
- a) a first polypeptide having the amino acid sequence set forth in SEQ ID NO:
- 423 comprising:
- i) a Wilms tumor-1 (WT1) peptide;
- ii) a β2-microglobulin (β2M) polypeptide;
- and
- iii) a peptide linker between the WT1 peptide and the β2M polypeptide, wherein the peptide linker comprises a Cys residue, and
- b) a second polypeptide having the amino acid sequence set forth in SEQ ID NO:
- 486 comprising:
- i) two variant IL-2 polypeptides;
- ii) a major histocompatibility complex (MHC) class I heavy chain polypeptide;
- and
- ii) an immunoglobulin (Ig) Fc polypeptide,
- wherein each heterodimer comprises a first disulfide bond formed between (i) the Cys residue in the peptide linker between the WT1 peptide and the β2M polypeptide, and (ii) a Cys residue in the MHC class I heavy chain polypeptide,
- wherein each heterodimer comprises a second disulfide bond formed between a Cys residue in the β2M polypeptide and a Cys residue in the MHC class I heavy chain polypeptide,
- wherein two disulfide bonds link the Ig Fc polypeptide of one heterodimer to the Ig Fc polypeptide of the other heterodimer.
12 more elements
A homodimer consisting of two heterodimers, wherein each heterodimer comprises:
- a) a first polypeptide having the amino acid sequence set forth in SEQ ID NO:
- 423 comprising:
- i) a Wilms tumor-1 (WT1) peptide;
- ii) a β2-microglobulin (β2M) polypeptide;
- and
- iii) a peptide linker between the WT1 peptide and the β2M polypeptide, wherein the peptide linker comprises a Cys residue, and
- b) a second polypeptide having the amino acid sequence set forth in SEQ ID NO:
- 486 comprising:
- i) two variant IL-2 polypeptides;
- ii) a major histocompatibility complex (MHC) class I heavy chain polypeptide;
- and
- ii) an immunoglobulin (Ig) Fc polypeptide,
- wherein each heterodimer comprises a first disulfide bond formed between (i) the Cys residue in the peptide linker between the WT1 peptide and the β2M polypeptide, and (ii) a Cys residue in the MHC class I heavy chain polypeptide,
- wherein each heterodimer comprises a second disulfide bond formed between a Cys residue in the β2M polypeptide and a Cys residue in the MHC class I heavy chain polypeptide, and
- wherein two disulfide bonds link the Ig Fc polypeptide of one heterodimer to the Ig Fc polypeptide of the other heterodimer.
12 more elements
Dependencies are inferred from the claim text.