Multivalent entrain-and-amplify immunotherapeutics for carcinoma

Abstract

The present invention provides a method of treating a cell proliferative disease such as cancer by providing to a subject in need thereof an immunogenic composition comprising plasmid and peptide(s) or analogues thereof. In embodiments of the present invention there is provided methods and compositions for inducing, entraining, and/or amplifying the immune response to MHC class-I restricted epitopes of carcinoma antigens to generate an effective anti-cancer immune response.

1 - 43 . (canceled) 
     
     
         44 . An immunogenic product comprising a plurality of compositions comprising one or more nucleic acid compositions and one or more peptide compositions; wherein the one or more nucleic acid compositions are capable of expressing two or more class I MHC restricted epitopes, wherein the two or more class I MHC restricted epitopes comprise a Melan-A epitope, or a cross reactive analogue thereof, and a Tyrosinase epitope, or a cross-reactive analogue thereof, and wherein the one or more peptide compositions comprise one or more class I MHC restricted epitopes, wherein the one or more class I MHC restricted epitopes comprise the Melan-A epitope, or a cross-reactive analogue thereof, or the Tyrosinase epitope, or a cross-reactive analogue thereof, or both. 
     
     
         45 . The immunogenic product of  claim 44 , wherein the Melan-A epitope is selected from Melan-A 26-35  (SEQ ID NO. 9) or an analogue thereof. 
     
     
         46 . The immunogenic product of  claim 45 , wherein the analogue of said Melan-A epitope is E{Nva}AGIGILTV (SEQ ID NO. 11). 
     
     
         47 . The immunogenic product of  claim 45 , wherein the analogue of said Melan-A epitope is the A27L analogue of the Melan-A 26-35  (SEQ ID NO. 9). 
     
     
         48 . The immunogenic product of  claim 44 , wherein the Tyrosinase epitope is selected from Tyrosinase 369-377  (SEQ ID NO. 10), or an analogue thereof. 
     
     
         49 . The immunogenic product of  claim 48 , wherein the analogue of said Tyrosinase epitope is YMDGTMSQ{Nva} (SEQ ID NO. 12). 
     
     
         50 . The immunogenic product of  claim 44 , wherein the one or more nucleic acid compositions is one composition. 
     
     
         51 . The immunogenic product of  claim 44 , wherein one molecule is capable of expressing the two or more class I MHC restricted epitopes. 
     
     
         52 . The immunogenic product of  claim 44 , wherein the one or more nucleic acid compositions comprise a sequence encoding the liberation sequence of SEQ ID NO. 15. 
     
     
         53 . The immunogenic product of  claim 44 , wherein the one or more nucleic acid compositions comprise a sequence encoding the immunogenic polypeptide of SEQ ID NO. 18. 
     
     
         54 . The immunogenic product of  claim 53 , wherein the one or more nucleic acid compositions comprise pSEM (SEQ ID NO:19). 
     
     
         55 . The immunogenic product of  claim 44 , further comprising at least one of:
 i. a nucleic acid molecule capable of expressing an SSX-2 class I MHC restricted epitope, or analogue thereof;   ii. a nucleic acid molecule capable of expressing an NY-ESO-1 class I MHC restricted epitope, or analogue thereof;   iii. a nucleic acid molecule capable of expressing a PRAME class I MHC restricted epitope, or analogue thereof;   iv. a nucleic acid molecule capable of expressing a PSMA class I MHC restricted epitope, or analogue thereof;   v. a peptide consisting essentially of an SSX-2 class I MHC restricted epitope, or analogue thereof;   vi. a peptide consisting essentially of an NY-ESO-1 class I MHC restricted epitope, or analogue thereof;   vii. a peptide consisting essentially of a PRAME class I MHC restricted epitope, or analogue thereof or   viii. a peptide consisting essentially of a PSMA class I MHC restricted epitope, or analogue thereof.   
     
     
         56 . The immunogenic product of  claim 55 , wherein the SSX-2 epitope is SSX-2 41-49  (SEQ ID NO. 1) or its analogue KVSEKIFYV (SEQ ID NO. 5);
 the NY-ESO-1 epitope is NY-ESO-1 157-165  (SEQ ID NO. 2) or its analogue S{Nva}LMWITQV (SEQ ID NO. 6);   the PRAME epitope is PRAME 425-433  (SEQ ID NO. 3) or its analogue S{Nva}LQHLIG{Nle} (SEQ ID NO. 7); or   the PSMA epitope is PSMA 288-297  (SEQ ID NO. 4) or its analogue GLPSIPVHPV (SEQ ID NO. 8).   
     
     
         57 . The immunogenic product of  claim 55 , wherein said one or more nucleic acid compositions comprise a plasmid selected from the group consisting of pSEM, pBPL and pRP12. 
     
     
         58 . A method of treating cancer comprising administering the product of  claim 44  to a patient in need thereof. 
     
     
         59 . The method of  claim 58 , wherein the cancer is a skin cancer, a melanoma, or a glioblastoma. 
     
     
         60 . The method of  claim 58 , further comprising a step of administering to a patient in need thereof a composition comprising:
 i) a nucleic acid molecule capable of expressing an SSX-2 class I MHC restricted epitope, or analogue thereof; or   ii) a nucleic acid molecule capable of expressing an NY-ESO-1 class I MHC restricted epitope, or analogue thereof; or   iii) a nucleic acid molecule capable of expressing an PRAME class I MHC restricted epitope, or analogue thereof; or   iv) a nucleic acid molecule capable of expressing an PSMA class I MHC restricted epitope, or analogue thereof; or   v) a peptide consisting essentially of an SSX-2 class I MHC restricted epitope, or analogue thereof;   vi) a peptide consisting essentially of an NY-ESO-1 class I MHC restricted epitope, or analogue thereof;   vii) a peptide consisting essentially of a PRAME class I MHC restricted epitope, or analogue thereof; or   viii) a peptide consisting essentially of a PSMA class I MHC restricted epitope, or analogue thereof.   
     
     
         61 . The method of  claim 58 , comprising administering the plurality of compositions for entraining and amplifying a T cell response in a subject. 
     
     
         62 . The method of  claim 58 , comprising administering the plurality of compositions for inducing an anti-cancer immune response in a subject.