Methods for modulating an immune response

A method of treating an individual having a cancer that expresses an HPV16 E7 antigen, the method comprising administering to the individual a combination of (i) an effective amount of an immune checkpoint inhibitor that targets PD-1, wherein the immune checkpoint inhibitor is an anti-PD-1 antibody, and (ii) an effective amount of a protein that is a homodimer of two multimeric polypeptides, wherein each multimeric polypeptide comprises:

• a) a first polypeptide comprising from N-terminus to C-terminus:
• i) an HPV16 E7 epitope comprising amino acid sequence YMLDLQPETT (SEQ ID NO:77);
• ii) a linker comprising amino acid sequence GGGGSGGGGSGGGGS (SEQ ID NO:207);
• and
• iii) a β2-microglobulin (β2M) polypeptide comprising the amino acid sequence set forth in SEQ ID NO:48;
• and
• b) a second polypeptide comprising:
• i) two copies of an IL-2 polypeptide, each copy comprising the amino acid sequence set forth in SEQ ID NO:49;
• ii) a second MHC polypeptide, wherein the second MHC polypeptide is an MHC class I heavy chain polypeptide comprising the amino acid sequence as set forth in SEQ ID NO:50;
• and
• iii) an immunoglobulin (Ig) Fc polypeptide, and
• wherein the multimeric polypeptides are joined to each other by one or more disulfide bonds that join the Ig Fc polypeptide of one multimeric polypeptide to the Ig Fc polypeptide of the other multimeric polypeptide, and
• wherein the immune checkpoint inhibitor and the protein are administered at the same time or at different times.