PD-1 and CTLA-4 dual inhibitor peptides
This disclosure provides peptides which have a strong affinity for the checkpoint receptor “programmed death 1” (PD-1). These peptides block the interaction of PD-1 with its ligand PD-L1 as well as the interaction of CTLA4 with CD86 and can therefore be used for various therapeutic purposes, such as inhibiting the progression of a hyperproliferative disorder, including cancer; treating infectious diseases; enhancing a response to vaccination; treating sepsis; and promoting hair re-pigmentation or lightening of pigmented skin lesions.
1. A peptide comprising the amino acid sequence CRRTSTGQISTLRVNITAPLSQ.
2. An expression construct encoding the peptide of claim 1 .
3. The expression construct of claim 2 , which is present in a CAR-T cell or an oncolytic virus.
4. A pharmaceutical composition comprising (a) the peptide of claim 1 and
(b) a pharmaceutically acceptable carrier.
5. The pharmaceutical composition of claim 4 , wherein the peptide is provided with a peptide carrier system selected from the group consisting of a microparticle, a polymeric nanoparticle, a liposome, a solid lipid nanoparticle, a hydrophilic mucoadhesive polymer, a thiolated polymer, a polymer matrix, a nanoemulsion, and a hydrogel.
6. The peptide of claim 1 , which comprises one or more modifications selected from the group consisting of a C-terminal amidation, an N-terminal acetylation, and a replacement of at least one L-amino acid with the corresponding D-amino acid.
7. The peptide of claim 6 , which comprises the C-terminal amidation.
8. The pharmaceutical composition of claim 4 , wherein the peptide comprises a C-terminal amidation.