Identification of immunogenic mhc class ii peptides for immune-based therapy

Abstract

The invention provides compositions, methods, and vaccines that may stimulate the immune system and that may be used for treating malignancies associated with overexpression of the HER3 protein. Such compositions include epitopes of the HER3 protein.

What is claimed is: 
     
         1 . An isolated peptide selected from the group consisting of p11-13 (Peptide 51-75): KLYERCEVVMGNLEIVLTGHNADLSFLQW (SEQ ID NO. 1), p81-83 (Peptide 401-425): SWPPHMHNFSVFSNLTTIGGRSLYN (SEQ ID NO. 2), p84-86 (Peptide 416-440): TTIGGRSLYNRGFSLLIMKNLNVTS (SEQ ID NO. 3), p12 (Peptide 56-70): CEVVMGNLEIVLTGH (SEQ ID NO. 4), p81 (Peptide 401-415): SWPPHMHNFSVFSNL (SEQ ID NO. 5), p84 (Peptide 416-430): TTIGGRSLYNRGFSL (SEQ ID NO. 6), and p91 (Peptide 451-465): AGRIYISANRQLCYH (SEQ ID NO. 7). 
     
     
         2 . An immunomodulating agent comprising one or more peptides of  claim 1 . 
     
     
         3 . A vaccine comprising one or more peptides of  claim 1  and a pharmaceutically acceptable salt. 
     
     
         4 . The vaccine of  claim 3  further comprising an adjuvant. 
     
     
         5 . A cell, wherein the cell has been contacted with one or more peptides of  claim 1 . 
     
     
         6 . The cell of  claim 5 , wherein said cell is an antigen presenting cell. 
     
     
         7 . The cell of  claim 5 , wherein said cell is a T cell. 
     
     
         8 . A method of eliciting an immune response in a subject comprising administering to the subject the composition of  claim 1 . 
     
     
         9 . A method of treating cancer in a subject comprising administering to the subject one or more peptides of  claim 1 . 
     
     
         10 . The method of  claim 9 , wherein said subject is a human and has cancer. 
     
     
         11 . The method of  claim 10 , wherein said cancer is selected from the group consisting of breast cancer, ovarian cancer, lung cancer, prostate cancer, colon cancer, melanoma, pancreatic cancer, gastrointestinal cancer, brain cancer, and any combination thereof. 
     
     
         12 . A method of activating a cell comprising contacting said cell with one or more peptides of  claim 1 . 
     
     
         13 . The method of  claim 12 , wherein said cell is an antigen presenting cell. 
     
     
         14 . The method of  claim 12 , wherein said cell is a T cell. 
     
     
         15 . A method of generating a peptide loaded, activated dendritic cells (DC) for use in immunotherapy, comprising:
 pulsing said DC with one or more peptide of  claim 1 ;   activating said DC with at least one TLR agonist.   
     
     
         16 . The method of  claim 15  comprising contacting said DC with an agent that elevates the intracellular calcium concentration in said DC. 
     
     
         17 . The method of  claim 15 , wherein said agent comprises a calcium ionophore. 
     
     
         18 . The method of  claim 15 , further comprising cryopreserving said DC, wherein when said DC is thawed, and said DC produces an effective amount of at least one cytokine to generate a T cell response. 
     
     
         19 . A cell generated from the method of  claim 15 . 
     
     
         20 . A vaccine comprising a cell generated from the method of  claim 15 . 
     
     
         21 . The vaccine of  claim 20 , wherein said vaccine is in a form of an injectable multi-dose vaccine. 
     
     
         22 . A method of eliciting an immune response in a mammal, comprising administering a population of cells generated from the method of  claim 20  to a mammal in need thereof. 
     
     
         23 . A method of treating a disease or disorder in a mammal, comprising administering a population of cells generated from the method of  claim 20  to a mammal in need thereof. 
     
     
         24 . A biomarker for detecting tumor progression in premalignant lesions of the gastroesophageal junction in a subject having Barrett's esophagus which comprises detecting overexpression of HER3 in said subject. 
     
     
         25 . A method of treating a patient who has lost anti-HER3 CD4+ Th1 comprising, administering to said patient at least one dose of an antigen-pulsed DC1 vaccine derived from said patient's monocytic dendritic cell (DC) precursors which are pulsed with HER3 MHC Class II immunogenic peptides wherein said peptides are selected from the group consisting of p12 (Peptide 56-70): CEVVMGNLEIVLTGH (SEQ ID NO: 4); p81 (Peptide 401-415): SWPPHMHNFSVFSNL (SEQ ID NO: 5); p84 (Peptide 416-430): TTIGGRSLYNRGFSL (SEQ ID NO: 6); and p91 (Peptide 451-465): AGRIYISANRQLCYH (SEQ ID NO: 7), and any combination thereof. 
     
     
         26 . The method of  claim 25 , wherein said patient has triple negative invasive breast cancer. 
     
     
         27 . A method of detecting anti-HER3 CD4+ Th1 loss in a patient, comprising,
 pulsing peripheral blood mononuclear cells derived from said patient with HER3 MHC Class II immunogenic peptides wherein said peptides are selected from the group consisting of p12 (Peptide 56-70): CEVVMGNLEIVLTGH (SEQ ID NO: 4); p81 (Peptide 401-415): SWPPHMHNFSVFSNL (SEQ ID NO: 5); p84 (Peptide 416-430): TTIGGRSLYNRGFSL (SEQ ID NO: 6); and p91 (Peptide 451-465): AGRIYISANRQLCYH (SEQ ID NO: 7), and any combination thereof; and   detecting immune response generated thereby.   
     
     
         28 . The method of  claim 28 , wherein said detecting of anti-HER3 CD4 Th1 response is measured by IFN-γ ELISpot assay