SYNTAC POLYPEPTIDES AND USES THEREOF

1 .- 78 . (canceled)

79 . A multimeric polypeptide comprising:

at least one heterodimer comprising:

a) a first polypeptide comprising:

i) a peptide epitope; 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, and

wherein the peptide epitope is an epitope present on a cancer cell.

80 . A multimeric polypeptide according to claim 79 , wherein the first or the second polypeptide comprises an immunoglobulin (Ig) Fc polypeptide.

81 . A multimeric polypeptide according to claim 80 , wherein the Ig Fc polypeptide is an IgG1 Fc polypeptide.

82 . A multimeric polypeptide according to claim 79 , wherein:

a) the first polypeptide comprises, in order from N-terminus to C-terminus:

i) the peptide epitope;

ii) the first MHC polypeptide; and

iii) at least one immunomodulatory domain; and

b) the second polypeptide comprises, in order from N-terminus to C-terminus:

i) the second MHC polypeptide; and

ii) an immunoglobulin (Ig) Fc polypeptide.

83 . A multimeric polypeptide according to claim 79 , wherein:

a) the first polypeptide comprises, in order from N-terminus to C-terminus:

i) the peptide epitope; and

ii) the first MHC polypeptide; and

b) the second polypeptide comprises, in order from N-terminus to C-terminus:

i) at least one immunomodulatory domain;

iii) the second MHC polypeptide; and

ii) an Ig Fc polypeptide.

84 . A multimeric polypeptide according to claim 79 , wherein:

a) the first polypeptide comprises, in order from N-terminus to C-terminus:

i) the peptide epitope; and

ii) the first MHC polypeptide; and

b) the second polypeptide comprises, in order from N-terminus to C-terminus:

i) the second MHC polypeptide; and

ii) the Ig Fc polypeptide; and

iii) at least one immunomodulatory domain.

85 . A multimeric polypeptide according to claim 79 , wherein:

a) the first polypeptide comprises, in order from N-terminus to C-terminus:

i) the peptide epitope; and

ii) the first MHC polypeptide; and

b) the second polypeptide comprises, in order from N-terminus to C-terminus:

i) the second MHC polypeptide; and

ii) at least one immunomodulatory domain.

86 . A multimeric polypeptide according to claim 79 , wherein:

a) the first polypeptide comprises, in order from N-terminus to C-terminus:

i) the peptide epitope; and

ii) the first MHC polypeptide; and

b) a second polypeptide comprises, in order from N-terminus to C-terminus:

i) at least one immunomodulatory domain; and

ii) the second MHC polypeptide.

87 . A multimeric polypeptide according to claim 79 , wherein:

a) the first polypeptide comprises, in order from N-terminus to C-terminus:

i) the peptide epitope;

ii) the first MHC polypeptide; and

iii) at least one immunomodulatory domain; and

b) the second polypeptide comprises:

i) the second MHC polypeptide.

88 . A multimeric polypeptide according to claim 79 , wherein the first MHC polypeptide is a β2-microglobulin polypeptide; and wherein the second MHC polypeptide is an MHC class I heavy chain polypeptide.

89 . A multimeric polypeptide according to claim 79 , wherein the at least one immunomodulatory polypeptide is selected from the group consisting of a cytokine, a 4-1BBL polypeptide, a B7-1 polypeptide; a B7-2 polypeptide, an ICOS-L polypeptide, an OX-40L polypeptide, a CD80 polypeptide, a CD86 polypeptide, a PD-L1 polypeptide, a FasL polypeptide, a PD-L2 polypeptide, and combinations thereof.

90 . A multimeric polypeptide according to claim 89 , wherein the at least one immunomodulatory domain has a naturally occurring polypeptide sequence.

91 . A multimeric polypeptide according to claim 89 , wherein the at least one immunomodulatory polypeptide comprises a cytokine.

92 . A multimeric polypeptide according to claim 89 , wherein the multimeric polypeptide comprises at least two immunomodulatory polypeptides, and wherein at least two of the immunomodulatory polypeptides are the same.

93 . A multimeric polypeptide according to claim 92 , wherein the 2 or more immunomodulatory polypeptides are in tandem.

94 . A multimeric polypeptide according to claim 79 , wherein the first polypeptide and the second polypeptide are covalently linked.

95 . A multimeric polypeptide according to claim 94 , wherein the covalent linkage is via a disulfide bond.

96 . A multimeric polypeptide according to claim 95 , wherein the first MHC polypeptide or a linker between the epitope and the first MHC polypeptide comprises an amino acid substitution to provide a first Cys residue, and the second MHC polypeptide comprises an amino acid substitution to provide a second Cys residue, and wherein the disulfide linkage is between the first and the second Cys residues.

97 . A multimeric polypeptide according to claim 79 , wherein the peptide epitope has a length of from about 4 amino acids to about 25 amino acids.

98 . A multimeric polypeptide according to claim 79 , wherein the first polypeptide comprises a linker between the peptide epitope and the first MHC polypeptide.

99 . A multimeric polypeptide according to claim 79 , wherein the first polypeptide comprises a linker between the first MHC polypeptide and the immunomodulatory polypeptide.

100 . A multimeric polypeptide according to claim 98 , wherein the linker comprises a serine and a glycine.

101 . A multimeric polypeptide according to claim 99 , wherein the linker comprises a serine and a glycine.

102 . A multimeric polypeptide according to claim 80 , wherein the multimeric polypeptide comprises a first and a second heterodimer, and

wherein the first and second heterodimers are covalently bound by one or more disulfide bonds between the Ig Fc polypeptides of the first and second heterodimers.

103 . A nucleic acid comprising a nucleotide sequence encoding a first or second polypeptide according to claim 79 , wherein the first or second polypeptide comprises at least one immunomodulatory domain.

104 . A nucleic acid according to claim 103 , wherein the multimeric polypeptide comprises a first and a second heterodimer, and

wherein the first and second heterodimers are covalently bound by one or more disulfide bonds between the Ig Fc polypeptides of the first and second heterodimers.

105 . A method of selectively modulating the activity of an epitope-specific T cell, the method comprising contacting the T cell with a multimeric polypeptide according to claim 79 , wherein said contacting selectively modulates the activity of the epitope-specific T cell.

106 . A method of selectively modulating the activity of an epitope-specific T cell according to claim 105 , wherein the multimeric polypeptide comprises a first and a second heterodimer, and

wherein the first and second heterodimers are covalently bound by one or more disulfide bonds between the Ig Fc polypeptides of the first and second heterodimers.

107 . A method of treating a patient having a cancer comprising administering to the patient an effective amount of a pharmaceutical composition comprising a multimeric polypeptide according to claim 79 .

108 . A method of treating a patient having a cancer according to claim 107 , herein the multimeric polypeptide comprises a first and a second heterodimer, and

wherein the first and second heterodimers are covalently bound by one or more disulfide bonds between the Ig Fc polypeptides of the first and second heterodimers.