CPC C07K 14/70539 (2013.01) [C07K 16/082 (2013.01); C12N 15/86 (2013.01); C07K 2317/34 (2013.01); C07K 2317/92 (2013.01); C12N 2730/10122 (2013.01)] | 18 Claims |
1. A T-cell modulatory multimeric polypeptide (TMMP) comprising:
at least one heterodimer comprising:
a) a first polypeptide comprising:
i) a hepatitis B virus (HBV) peptide epitope, wherein the HBV peptide has a length of at least 4 amino acids; and
ii) first major histocompatibility complex (MHC) polypeptide;
b) a second polypeptide comprising a second MHC polypeptide and an immunoglobulin (Ig) Fc polypeptide, and
c) one or more immunomodulatory polypeptides that modulates a CD8+T cell that is specific for the HBV epitope,
wherein the first and/or the second polypeptide comprises the immunomodulatory polypeptide, and
wherein the first MHC polypeptide is β2-microglobulin (β2M) polypeptide; and wherein the second MHC polypeptide is an MHC class I heavy chain polypeptide,
wherein at least one of the one or more immunomodulatory polypeptides is a variant immunomodulatory polypeptide that binds to a cognate co-immunomodulatory polypeptide and exhibits reduced affinity to the cognate co-immunomodulatory polypeptide compared to the affinity of a corresponding wild-type immunomodulatory polypeptide for the cognate co-immunomodulatory polypeptide.
|