Activation and expansion of nkg2c+ nk cells

Abstract

The invention relates to an isolated peptide for use as a medicament, wherein said peptide has 9 to 30 amino acids and comprises or consists of an amino acid sequence according to SEQ ID NO 1 (VMAPRTLXL), wherein X is an amino acid with a hydrophobic side chain (A, I, L, F, V, P, G), preferably V, L, I or F. The invention further relates to the peptide of the invention for use as a medicament to expand and/or activate NKG2C+ natural killer (NK) cells. The invention further relates to the peptide of the invention for use in the treatment and/or prevention of a medical condition associated with pathogenic cells expressing HLA-E and a peptide comprising an amino acid sequence according to SEQ ID NO 1 or 2. Additionally, the invention relates to a genetically modified virus encoding a peptide comprising or consisting of a polypeptide of the invention for use as a medicament to expand and/or activate NKG2C+ natural killer (NK) cells.

What is claimed is: 
     
         1 . A method of treating a subject having or being at risk of developing an active human cytomegalovirus (HCMV) infection, the method comprising administering to said subject an effective amount of an isolated peptide of 9 to 30 amino acids comprising an amino acid sequence according to SEQ ID NO: 1 (VMAPRTLXL), wherein X is an amino acid with a hydrophobic side chain (A, I, L, F, V, P, G), wherein the method expands and/or activates NKG2C+ natural killer (NK) cells. 
     
     
         2 . The method according to  claim 1 , wherein said peptide comprises an amino acid sequence consisting of SEQ ID NO 2 (VMAPRTLFL). 
     
     
         3 . The method according to  claim 1 , wherein the treatment inhibits reactivation of human HCMV. 
     
     
         4 . The method according to  claim 1 , wherein the treatment reduces viral titers in an individual infected with HCMV. 
     
     
         5 . The method according to  claim 1 , wherein the subject has leukemia and the treatment inhibits reactivation of HCMV infections in subjects having received hematopoietic stem cell transplantation. 
     
     
         6 . The method according to  claim 1 , wherein the peptide is administered in combination with an adjuvant that enhances production of, or comprises, IL-15, IL-12 and/or IL-18. 
     
     
         7 . The method according to  claim 1 , wherein the peptide is administered in combination with a check point inhibitor. 
     
     
         8 . The method according to  claim 7 , wherein the peptide is administered in combination with an inhibitor of a receptor selected from the group consisting of LILRB1, inhibitory KIRs, NKG2A, PD-1, CTLA-4, TIM-3, TIGIT and LAG-3. 
     
     
         9 . The method according to  claim 1 , wherein the peptide is administered by a vector comprising or encoding the peptide according to  claim 1 , wherein the peptide is encoded by a nucleic acid molecule operably linked to a promoter for expression in mammalian subjects. 
     
     
         10 . The method according to  claim 9 , wherein the vector is a genetically modified virus selected from the group consisting of attenuated HCMV, vaccinia virus, adenovirus, adeno-associated virus, retrovirus, and lentivirus. 
     
     
         11 . The method according to  claim 1 , the method comprising administering to said subject an effective amount of a genetically modified virus encoding a peptide comprising or consisting of a polypeptide according to  claim 1 .