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US 2025/0092113 A1Published application
Multimeric T-Cell Modulatory Polypeptides and Methods of Use Thereof
AssigneeCue Biopharma, Inc.
InventorsRonald D. Seidel, III, Rodolfo J. Chaparro
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Abstract
The present disclosure provides T-cell modulatory multimeric polypeptides that comprise an immunomodulatory polypeptide, an epitope-presenting peptide, and class I MHC polypeptides. 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.
Claims21
-35. (canceled)
A T-cell modulatory multimeric polypeptide (TMMP) comprising:
- at least one heterodimer comprising:
- a) a first polypeptide comprising:
- i) a cancer-associated peptide epitope, wherein the epitope is associated with a cancer that expresses NY-ESO-1, and wherein the peptide epitope has a length of from 8 amino acids to 16 amino acids;
- and
- ii) first major histocompatibility complex (MHC) polypeptide;
- b) a second polypeptide comprising a second MHC polypeptide;
- and
- c) at least one immunomodulatory polypeptide,
- wherein the first and/or the second polypeptide comprises the immunomodulatory polypeptide,
- wherein the first or the second polypeptide comprises an immunoglobulin (Ig) Fc polypeptide, and
- wherein the first class I MHC polypeptide is a β2-microglobulin (β2M) polypeptide and the second class I MHC polypeptide is an MHC class I heavy chain polypeptide, and
- wherein the TMMP comprises (a) a first disulfide bond formed between (i) a Cys residue in a linker between the peptide epitope and the β2M polypeptide, and (ii) a Cys residue in the MHC class I heavy chain polypeptide;
- and (b) 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.
10 more elements
A T-cell modulatory multimeric polypeptide (TMMP) comprising:
- at least one heterodimer comprising:
- a) a first polypeptide comprising:
- i) a cancer-associated peptide epitope, wherein the epitope is associated with a cancer that expresses a melanoma-associated antigen (MAGE), and wherein the peptide epitope has a length of from 8 amino acids to 16 amino acids;
- and
- ii) first major histocompatibility complex (MHC) polypeptide;
- b) a second polypeptide comprising a second MHC polypeptide, and
- c) at least one immunomodulatory polypeptide,
- wherein the first and/or the second polypeptide comprises the immunomodulatory polypeptide,
- wherein the first or the second polypeptide comprises an immunoglobulin (Ig) Fc polypeptide, and
- wherein the first class I MHC polypeptide is a β2-microglobulin (β2M) polypeptide and the second class I MHC polypeptide is an MHC class I heavy chain polypeptide, and
- wherein the TMMP comprises (a) a first disulfide bond formed between (i) a Cys residue in a linker between the peptide epitope and the β2M polypeptide, and (ii) a Cys residue in the MHC class I heavy chain polypeptide;
- and (b) 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.
9 more elements
A T-cell modulatory multimeric polypeptide (TMMP) comprising:
- at least one heterodimer comprising:
- a) a first polypeptide comprising:
- i) a peptide epitope, wherein the epitope is presented by a coronavirus-encoded polypeptide, wherein the peptide epitope has a length of from 8 amino acids to 16 amino acids;
- and
- ii) first major histocompatibility complex (MHC) polypeptide;
- b) a second polypeptide comprising a second MHC polypeptide;
- and
- c) at least one immunomodulatory polypeptide,
- wherein the first and/or the second polypeptide comprises the immunomodulatory polypeptide,
- wherein the first or the second polypeptide comprises an immunoglobulin (Ig) Fc polypeptide, and
- wherein the first class I MHC polypeptide is a β2-microglobulin (β2M) polypeptide and the second class I MHC polypeptide is an MHC class I heavy chain polypeptide, and
- wherein the TMMP comprises (a) a first disulfide bond formed between (i) a Cys residue in a linker between the peptide epitope and the β2M polypeptide, and (ii) a Cys residue in the MHC class I heavy chain polypeptide;
- and (b) 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.
10 more elements
A T-cell modulatory multimeric polypeptide (TMMP) comprising:
- at least one heterodimer comprising:
- a) a first polypeptide comprising:
- i) a peptide epitope, wherein the epitope is presented by a cytomegalovirus-encoded polypeptide, and wherein the peptide epitope has a length of from 8 amino acids to 16 amino acids;
- and
- ii) first major histocompatibility complex (MHC) polypeptide;
- b) a second polypeptide comprising a second MHC polypeptide;
- and
- c) at least one immunomodulatory polypeptide,
- wherein the first and/or the second polypeptide comprises the immunomodulatory polypeptide,
- wherein the first or the second polypeptide comprises an immunoglobulin (Ig) Fc polypeptide, and
- wherein the first class I MHC polypeptide is a β2-microglobulin (β2M) polypeptide and the second class I MHC polypeptide is an MHC class I heavy chain polypeptide, and
- wherein the TMMP comprises (a) a first disulfide bond formed between (i) a Cys residue in a linker between the peptide epitope and the β2M polypeptide, and (ii) a Cys residue in the MHC class I heavy chain polypeptide;
- and (b) 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.
10 more elements
Dependencies are inferred from the claim text.