Scaffolds with stabilized MHC molecules for immune-cell manipulation

An artificial antigen presenting cell (aAPC) scaffold comprising:

• a polymeric backbone to which are attached:
• i. at least two different gamma-chain receptor cytokines selected from the group consisting of IL-21, IL-2, IL-15, IL-4, IL-7 and IL-9, wherein the cytokines comprise at least IL-21, and
• ii. at least one MHC class I molecule,
• wherein the at least one MHC class I molecule comprises a heavy chain comprising an alpha-1 domain and an alpha-2 domain connected by a disulfide bridge formed between a mutant cysteine residue positioned in the alpha-1 domain and a mutant cysteine residue positioned in the alpha-2 domain,
• wherein the heavy chain comprises an amino acid sequence selected from:
• a. SEQ ID NO:
• 1, or
• b. an amino acid sequence having at least 85% sequence identity to the sequence in (a), and
• wherein said amino acid sequence comprises the mutant cysteine residue positioned in the alpha-1 domain and the mutant cysteine residue positioned in the alpha-2 domain,
• wherein the spatial distance between the mutant cysteine residue positioned in the alpha-1 domain and the mutant cysteine residue positioned in the alpha-2 domain is between 2 and 10 angstroms,
• wherein the mutant cysteine residue in the alpha-1 domain is at amino acid residue 84 or 85 and the mutant cysteine residue positioned in the alpha-2 domain is at amino acid residue 139, relative to SEQ ID NO:
• 1.