Hmgn polypeptides as immune enhancers and hmgn antagonists as immune suppressants

Abstract

A method of enhancing an antigen-specific immune response in a host comprising administering to the host an HMGN polypeptide comprising at least one of HMGN1, HMGN3a, HMGN3b, HMGN4, Nsbp1, or a functional fragment thereof, in an amount effective to enhance an antigen-specific immune response; as well as a pharmaceutical composition comprising an HMGN polypeptide comprising at least one of HMGN1, HMGN3a, HMGN3b, HMGN4, Nsbp1, or a functional fragment thereof, and an antigen, or nucleic acids encoding such molecules; and related methods and compositions.

1 . A pharmaceutical composition comprising:
 an HMGN polypeptide comprising HMGN1 (SEQ ID NO: 1), HMGN3a (SEQ ID NO: 2), HMGN3b (SEQ ID NO: 3), HMGN4 (SEQ ID NO: 4), Nsbp1 (SEQ ID NO: 5), or a functional fragment thereof, and   an antigen.   
     
     
         2 . The pharmaceutical composition of  claim 1 , wherein the HMGN polypeptide and the antigen are provided as a fusion protein or conjugate. 
     
     
         3 . The pharmaceutical composition of  claim 1 , wherein the pharmaceutical composition comprises two or more different HMGN polypeptides, selected from HMGN1 (SEQ ID NO: 1), HMGN3a (SEQ ID NO: 2), HMGN3b (SEQ ID NO: 3), HMGN4 (SEQ ID NO: 4), Nsbp1 (SEQ ID NO: 5), or functional fragments thereof. 
     
     
         4 . The pharmaceutical composition of  claim 1 , wherein the HMGN polypeptide comprises HMGN1 (SEQ ID NO: 1). 
     
     
         5 . The pharmaceutical composition of  claim 1 , wherein the antigen comprises a tumor antigen. 
     
     
         6 . The pharmaceutical composition of  claim 1 , wherein the antigen comprises two or more different antigens. 
     
     
         7 . The pharmaceutical composition of  claim 1 , wherein the antigen is selected from Ig-idiotype of B cell lymphoma; mutant cyclin-dependent kinase 4 of melanoma; Pmel-17 (gp100) of melanoma; MART-1 (Melan-A) of melanoma; p15 polypeptide of melanoma; tyrosinase of melanoma; MAGE 1, 2 and 3 of melanoma, thyroid medullary, small cell lung cancer, colon and/or bronchial squamous cell cancer; BAGE of bladder, melanoma, breast, and squamous-cell carcinoma; gp75 of melanoma; oncofetal antigen of melanoma; muci mucin of breast, pancreas, and ovarian cancer; GM2 and GD2 gangliosides of melanoma; mutant p53 of carcinoma; mutant ras of colon cancer; HER21neu proto-onco-gene of breast carcinoma; human papilloma virus polypeptides of squamous cell cancers of cervix and esophagus; and combinations thereof. 
     
     
         8 . The pharmaceutical composition of  claim 1 , further comprising a pharmaceutically active agent. 
     
     
         9 . The pharmaceutical composition of  claim 8 , wherein the pharmaceutically active agent is a chemotherapeutic agent selected from asparaginase, busulfan, carboplatin, cisplatin, daunorubicin, doxorubicin, fluorouracil, gemcitabine, hydroxyurea, methotrexate, paclitaxel, rituximab, vinblastine, vincristine, bacillus calmette-guerin (BCG), IL-2, an interferon, GM-CSF, and trastuzumab. 
     
     
         10 . A composition comprising:
 a nucleic acid encoding an HMGN polypeptide comprising HMGN1 (SEQ ID NO: 1), HMGN3a (SEQ ID NO: 2), HMGN3b (SEQ ID NO: 3), HMGN4 (SEQ ID NO: 4), Nsbp1 (SEQ ID NO: 5), or a functional fragment thereof, and   a nucleic acid encoding an antigen.   
     
     
         11 . The composition of  claim 10 , wherein the nucleic acid encoding the HMGN polypeptide and the nucleic acid encoding the antigen comprise a single nucleic acid encoding a fusion protein of the HMGN polypeptide and the antigen. 
     
     
         12 . The composition of  claim 10 , wherein the nucleic acid encoding the HMGN polypeptide is at least one sequence selected from any one of SEQ ID NOs: 6-10, and a degenerate nucleic acid sequence encoding the same amino acid sequence. 
     
     
         13 . A recombinant expression vector comprising a nucleic acid encoding an HMGN polypeptide comprising HMGN1 (SEQ ID NO: 1), HMGN3a (SEQ ID NO: 2), HMGN3b (SEQ ID NO: 3), HMGN4 (SEQ ID NO: 4), Nsbp1 (SEQ ID NO: 5), or a functional fragment thereof, and a nucleic acid encoding an antigen, which expression vector permits expression of an HMGN mRNA or polypeptide by a host cell.