Pdl1 peptides for use in cancer vaccines

Abstract

The present invention relates to a PD-L1 peptide fragment, useful in cancer therapies as well as PD-L1 peptide fragments for use in a method for treatment or prevention of a cancer, when administered simultaneously or sequentially with an additional cancer therapy.

1 - 17 . (canceled) 
     
     
         18 . A PD-L1 peptide fragment, or a pharmaceutically acceptable salt thereof, having the formula: 
       
         
           
                 
                 
               
                     
                   X 1 VILGAILLCLGVALTFIX 2   
                 
             
                
               
            
           
         
         wherein 
         N-terminal X 1  is selected from a group consisting of L, HL, THL, RTHL (SEQ ID NO: 
         79), ERTHL (SEQ ID NO: 80), NERTHL (SEQ ID NO: 81), or is absent, 
         C-terminal X 2  is selected from a group consisting of F, FR, FRL, FRLR (SEQ ID NO: 82), FRLRK (SEQ ID NO: 83), FRLRKG (SEQ ID NO: 84), FRLRKGR (SEQ ID NO: 85), FRLRKGRM (SEQ ID NO: 86), FRLRKGRMM (SEQ ID NO: 87), FRLRKGRMMD (SEQ ID NO: 88), or is absent, 
         provided that if X 1  is absent then X 2  is not FRLRKG (SEQ ID NO: 84), and provided that if X 1  is NERTHL (SEQ ID NO: 81) then X 2  is not FRLR (SEQ ID NO: 82), 
         wherein the C-terminal amino acid may also comprise the amide. 
       
     
     
         19 . The peptide fragment of  claim 18 , wherein the peptide fragment has the amino acid sequence of RTHLVILGAILLCLGVALTFIFRLRKGR (SEQ ID NO: 52) including a C terminal amino acid or amide. 
     
     
         20 . The peptide fragment of  claim 18 , wherein the peptide fragment is selected from the group consisting of:
 NERTHLVILGAILLCLGVALTFIFRLRKGRMMD-OH (SEQ ID NO: 77);   NERTHLVILGAILLCLGVALTFIFRLRKGRMMD-NH 2  (SEQ ID NO: 77 with C terminal amide);   RTHLVILGAILLCLGVALTFIFRLRKGR-OH (SEQ ID NO: 52);   RTHLVILGAILLCLGVALTFIFRLRKGR-NH 2  (SEQ ID NO: 52 with C terminal amide);   NERTHLVILGAILLCLGVALTFI-OH (SEQ ID NO: 67);   NERTHLVILGAILLCLGVALTFI-NH 2  (SEQ ID NO: 67 with C terminal amide);   VILGAILLCLGVALTFI-OH (SEQ ID NO: 2); and   VILGAILLCLGVALTFI-NH 2  (SEQ ID NO: 2 with C terminal amide), or   a pharmaceutically acceptable salt thereof.   
     
     
         21 . The peptide fragment of  claim 18 , wherein the peptide fragment is selected from the group consisting of:
 NERTHLVILGAILLCLGVALTFIFRLRKGRMMD-OH (SEQ ID NO: 77);   RTHLVILGAILLCLGVALTFIFRLRKGR-OH (SEQ ID NO: 52); and   RTHLVILGAILLCLGVALTFIFRLRKGR-NH 2  (SEQ ID NO: 52 with C terminal amide).   
     
     
         22 . A composition comprising the PD-L1 peptide fragment of  claim 18 . 
     
     
         23 . The composition of  claim 22 , further comprising one or more of a pharmaceutically acceptable additive, a preservative, and an adjuvant. 
     
     
         24 . The composition of  claim 23 , wherein the adjuvant is selected from the group consisting of bacterial DNA based adjuvants, oil/surfactant based adjuvants, viral dsRNA based adjuvants, imidazochinilines, and a Montanide ISA adjuvant. 
     
     
         25 . A method of treating a clinical condition characterized by expression of PD-L1, the method comprising administering to an individual suffering from said clinical condition an effective amount of: the peptide fragment of  claim 18 ; or a PD-L1 peptide fragment having the formula: FMTYWHLLNAFTVTVPKDL (SEQ ID NO: 89) wherein the C-terminal amino acid also comprises the amide, or a pharmaceutically acceptable salt. 
     
     
         26 . The method of  claim 25 , wherein the clinical condition is a cancer where PD-L1 is expressed. 
     
     
         27 . The method of  claim 26 , wherein the cancer is a tumor. 
     
     
         28 . The method of  claim 25 , wherein the clinical condition is an infectious disease, e.g. an intracellular infection, for example an intracellular infection with a pathogen selected from the group consisting of L. monocytogenes and plasmodium, or a viral infection, for example an infection with a virus selected from the group consisting of HIV and hepatitis. 
     
     
         29 . The method of  claim 25 , wherein the clinical condition is an autoimmune disease, such as diabetes, SLE and sclerosis. 
     
     
         30 . The method of  claim 25 , further comprising simultaneously or sequentially administering to the individual an effective amount of an additional cancer therapy. 
     
     
         31 . The method of  claim 30 , wherein the additional cancer therapy is a cytokine therapy, a T-cell therapy, an NK therapy, an immune system checkpoint inhibitor, chemotherapy, radiotherapy, immunostimulating substances, gene therapy, antibodies and/or dendritic cells. 
     
     
         32 . The method of  claim 30 , wherein the additional cancer therapy is selected from the group consisting of Actimide, Azacitidine, Azathioprine, Bleomycin, Carboplatin, Capecitabine, Cisplatin, Chlorambucil, Cyclophosphamide, Cytarabine, Daunorubicin, Docetaxel, Doxifluridine, Doxorubicin, Epirubicin, Etoposide, Fludarabine, Fluorouracil, Gemcitabine, Hydroxyurea, Idarubicin, Irinotecan, Lenalidomide, Leucovorin, Mechlorethamine, Melphalan, Mercaptopurine, Methotrexate, Mitoxantrone, Nivolumab, Oxaliplatin, Paclitaxel, Pembrolizumab, Pemetrexed, Revlimid, Temozolomide, Teniposide, Thioguanine, Valrubicin, Vinblastine, Vincristine, Vindesine and Vinorelbine. 
     
     
         33 . A kit-of parts comprising:
 a) the composition of  claim 22 , and   b) a composition comprising at least one second active ingredient, wherein the second active ingredient is selected from the group consisting of an immunostimulating compound e.g. IL-2 and/or IL-21, and an anti-cancer agent e.g. Actimide, Azacitidine, Azathioprine, Bleomycin, Carboplatin, Capecitabine, Cisplatin, Chlorambucil, Cyclophosphamide, Cytarabine, Daunorubicin, Docetaxel, Doxifluridine, Doxorubicin, Epirubicin, Etoposide, Fludarabine, Fluorouracil, Gemcitabine, Hydroxyurea, Idarubicin, Irinotecan, Lenalidomide, Leucovorin, Mechlorethamine, Melphalan, Mercaptopurine, Methotrexate, Mitoxantrone, nivolumab, Oxaliplatin, Paclitaxel, pembrolizumab, Pemetrexed, Revlimid, Temozolomide, Teniposide, Thioguanine, Valrubicin, Vinblastine, Vincristine, Vindesine and Vinorelbine.   
     
     
         34 . The kits-of-parts of  claim 33 , wherein the provided compositions are to be administered simultaneously or sequentially.