Methods and compositions relating to p62 for the treatment and prophylaxis of cancer

Abstract

Provided herein are novel p62 compositions for the prophylaxis and treatment of cancer and related methods. The invention also provides modified p62 compositions that increase the anti-cancer activity of p62.

What is claimed is: 
     
         1 . A method to treat, alleviate, ameliorate, relieve, delay onset of, inhibit progression of, reduce severity of, and/or reduce incidence of one or more symptoms of a cancer in a subject comprising:
 administering to said subject an agent comprising:
 a p62/SQSTM1 polypeptide at least 90% identical to SEQ ID NO. 2; or, 
 a p62/SQSTM1 nucleic acid that encodes a polypeptide at least 90% identical to SEQ ID NO: 2; and, 
   stimulating the immune defense mechanism to attack neoplastic cells in said subject.   
     
     
         2 . The method according to  claim 1 , wherein said p62/SQSTM1 polypeptide or p62/SQSTM1 encoding nucleic acid further comprises a fusion polypeptide or nucleic acid encoding for a fusion polypeptide, respectively. 
     
     
         3 . The method according to  claim 1 , further comprising administering an adjuvant to said subject. 
     
     
         4 . The method according to  claim 3 , wherein said adjuvant is selected from the group consisting of: gel-type, microbial, particulate, oil-emulsion, surfactant-based, and synthetic adjuvant. 
     
     
         5 . The method according to  claim 1 , further comprising administering one or more co-stimulatory components. 
     
     
         6 . The method according to  claim 5 , wherein said one or more co-stimulatory components is selected from the group consisting of: a cell surface protein, a cytokine, a chemokine, and a signaling molecule. 
     
     
         7 . The method according to  claim 1 , further comprising administering one or more molecules that block suppressive or negative regulatory immune mechanisms. 
     
     
         8 . The method according to  claim 7 , wherein said one or more molecules that block suppressive or negative regulatory immune mechanisms is selected from the group consisting of: anti-CTLA-4 antibody, anti-CD25 antibody, anti-CD4 antibody, and IL13Ra2-Fc. 
     
     
         9 . The method according to  claim 1 , further comprising administering one or more anticancer therapies to said subject. 
     
     
         10 . The method according to  claim 9 , wherein said one or more anticancer therapies is selected from the group consisting of: a chemotherapeutic molecule, radiation, an anti-angiogenic molecule, an antibody, and a biological agent. 
     
     
         11 . The method according to  claim 10 , wherein said chemotherapeutic molecule is selected from the group consisting of: cyclophosphamide, doxorubicin, paclitaxel, docetaxel, vinblastin, methotrexate, navelbine, capecitabine, mitomycin C, and 5-fluorouracil. 
     
     
         12 . The method according to  claim 1 , wherein said cancer is solid tumor cancer. 
     
     
         13 . The method according to  claim 12 , wherein said solid tumor cancer is selected from the group consisting of: breast cancer, lung cancer, prostate cancer, gastric cancer, colorectal cancer, skin cancer, a cancer of the head and neck, bronchus cancer, pancreatic cancer, urinary bladder cancer, brain cancer, central nervous system cancer, peripheral nervous system cancer, esophageal cancer, cancer of the oral cavity or pharynx, liver cancer, kidney cancer, testicular cancer, biliary tract cancer, small bowel or appendix cancer, ovarian cancer, uterine cancer, salivary gland cancer, thyroid gland cancer, adrenal gland cancer, osteosarcoma, chondrosarcoma, and sarcoma. 
     
     
         14 . The method according to  claim 1 , wherein said cancer is cancer of the hematologic tissues. 
     
     
         15 . The method according to  claim 1 , wherein said subject is selected from the group consisting of: a subject diagnosed with cancer, a subject previously treated for cancer, a subject with a family history of cancer, and a subject predisposed to cancer. 
     
     
         16 . The method according to  claim 1 , wherein said agent comprises a p62/SQSTM1 encoding nucleic acid, and wherein said p62 encoding nucleic acid further comprises a plasmid. 
     
     
         17 . The method according to  claim 16  further comprising a strategy for improving the efficiency of nucleic acid-based immunization. 
     
     
         18 . The method according to  claim 17 , wherein said strategy is selected from the group consisting of: optimizing at least one codon, in vivo electroporation, incorporation of a CpG stimulatory motif, including a sequence for targeting of the endocytic or ubiquitin-processing pathways, including a Marek's disease virus type 1 VP22 sequence, including a prime-boost regimen, and a mucosal delivery vector. 
     
     
         19 . A method to treat, alleviate, ameliorate, relieve, delay onset of, inhibit progression of, reduce severity of, and/or reduce incidence of one or more symptoms of a cancer in a subject comprising:
 administering to said subject an agent comprising:
 at least 30 amino acids of a p62/SQSTM1 polypeptide; or, 
 a p62/SQSTM1 encoding nucleic acid, wherein said p62/SQSTM1 encoding nucleic acid encodes at least 30 amino acids of a p62/SQSTM1 polypeptide; and, 
   stimulating the immune defense mechanism to attack neoplastic cells in said subject.   
     
     
         20 . A method to treat, alleviate, ameliorate, relieve, delay onset of, inhibit progression of, reduce severity of, and/or reduce incidence of one or more symptoms of a cancer in a subject comprising:
 administering to said subject an agent comprising:
 a p62/SQSTM1 polypeptide with at least one or more domain deletions; or, 
 a p62/SQSTM1 nucleic acid that encodes a polypeptide with at least one or more domain deletions; and, 
   stimulating the immune defense mechanism to attack neoplastic cells in said subject.