Cancer immunotherapy by delivering class ii mhc antigens using a vlp-replicon

Abstract

Described herein is a method of preventing or treating a disease in a mammalian subject, comprising administering to the subject who is in need thereof an effective dosage of a pharmaceutical composition comprising a virus like particle (VLP) comprising: an alphavirus replicon comprising a recombinant polynucleotide, wherein the polynucleotide comprises a sequence encoding both subunits of a human class II major histocompatibility antigen, a retroviral gag protein, and a fusogenic envelope protein, wherein the VLP does not contain an alphavirus structural protein gene.

1 . A virus like particle (VLP) comprising:
 a. an alphavirus replicon comprising a recombinant polynucleotide, wherein the polynucleotide comprises a sequence encoding both subunits of a human class II major histocompatibility antigen and a sequence encoding an antigen specific to a diseased cell;   b. a retroviral gag protein, and   c. a fusogenic envelope protein,   
       wherein the VLP does not contain an alphavirus structural protein gene. 
     
     
         2 . The VLP of  claim 1 , wherein the alphavirus replicon comprises nucleic acid sequence of Sindbis virus or Venezuelan equine encephalitis virus. 
     
     
         3 . The VLP of  claim 1 , wherein the VLP does not comprise or express a retroviral pol gene. 
     
     
         4 . The VLP of  claim 1 , comprising a first and a second polynucleotide, wherein the alphavirus replicon is encoded by the first polynucleotide and the retroviral gag protein is encoded by the second polynucleotide, and wherein the first and the second polynucleotide are not covalently connected and are not operationally linked. 
     
     
         5 . The VLP of  claim 1 , wherein the fusogenic envelope protein is a glycoprotein, or fragment or derivative thereof. 
     
     
         6 . The VLP of  claim 1 , wherein the antigen specific to a diseased cell is a tumor-specific antigen. 
     
     
         7 . The VLP of  claim 6 , wherein the tumor-specific antigen is selected from the group consisting of Alpha fetoprotein (AFP), CA15-3, CA27-29, CA19-9, CA-125, Calcitonin, Calretinin, Carcinoembryonic antigen, CD34, CD99, CD117, Chromogranin, Cytokeratin, Desmin, Epithelial membrane protein (EMA), Factor VIII, CD31 FL1, Glial fibrillary acidic protein (GFAP), Gross cystic disease fluid protein (GCDFP-15), HMB-45, Human chorionic gonadotropin (hCG), inhibin, keratin, lymphocyte marker, MART-1 (Melan-A), Myo D1, muscle-specific actin (MSA), neurofilament, neuron-specific enolase (NSE), placental alkaline phosphatase (PLAP), prostate-specific antigen, PTPRC (CD45), S100 protein, smooth muscle actin (SMA), synaptophysin, thyroglobulin, thyroid transcription factor-1, Tumor M2-PK, vimentin, CD80, CD28, CD30, CD13, CD15, CD20, CD25, and CD10. 
     
     
         8 . The VLP of  claim 1 , wherein the tumor specific antigen and the human class II major histocompatibility antigen are both encoded by the alphavirus replicon. 
     
     
         9 . (canceled) 
     
     
         10 . (canceled) 
     
     
         11 . (canceled) 
     
     
         12 . The VLP of  claim 1 , wherein the fusogenic envelope protein binds specifically to a tumor cell. 
     
     
         13 . The VLP of  claim 1 , wherein the antigen specific to a diseased cell is expressed by a gene of an infectious virus. 
     
     
         14 . (canceled) 
     
     
         15 . (canceled) 
     
     
         16 . (canceled) 
     
     
         17 . A pharmaceutical composition comprising the VLP of  claim 1 . 
     
     
         18 . (canceled) 
     
     
         19 . A method of preventing or treating a disease in a mammalian subject, comprising administering to the subject who is in need thereof an effective dosage of a pharmaceutical composition of  claim 17 . 
     
     
         20 . (canceled) 
     
     
         21 . The method of  claim 19 , wherein the class II major histocompatibility antigen (class II MHC antigen) encoded by the VLP differs from the class II MEW antigen of the mammalian subject. 
     
     
         22 . The method of  claim 19 , wherein the pharmaceutical composition induces tumor-specific immunity. 
     
     
         23 . The method of  claim 19 , wherein the mammalian subject is a cancer patient having a solid tumor derived from a cancer selected from the group consisting of breast, cervical, prostate, ovary, renal carcinoma, lung, gastric, pancreas, glioblastoma, and colorectal cancers. 
     
     
         24 . The method of  claim 19 , wherein the antigen specific to a diseased cell is a tumor-specific antigen that comprises a polypeptide selected from the group consisting of alpha fetoprotein (AFP), CA15-3, CA27-29, CA19-9, CA-125, calcitonin, calretinin, carcinoembryonic antigen, chromogranin, cytokeratin, desmin, epithelial membrane protein (EMA), Factor VIII, FL1, glial fibrillary acidic protein (GFAP), gross cystic disease fluid protein (GCDFP-15), HMB-45, human chorionic gonadotropin (hCG), inhibin, keratin, lymphocyte marker, MART-1 (Melan-A), Myo D1, muscle-specific actin (MSA), neurofilament, neuron-specific enolase (NSE), placental alkaline phosphatase (PLAP), prostate-specific antigen, S100 protein, smooth muscle actin (SMA), synaptophysin, thyroglobulin, thyroid transcription factor-1, tumor M2-PK, vimentin, cluster of differention 10 (CD10), CD13, CD15, CD20, CD25, CD30, CD31, CD34, CD45 (PTPRC), CD99, CD 117, and a fragment thereof. 
     
     
         25 . (canceled) 
     
     
         26 . The method of  claim 19 , wherein the disease is an infectious disease. 
     
     
         27 . The method of  claim 26 , wherein the recombinant polynucleotide further comprises a sequence of an infectious virus. 
     
     
         28 . (canceled) 
     
     
         29 . (canceled) 
     
     
         30 . (canceled) 
     
     
         31 . The method of  claim 19 , wherein the pharmaceutical composition is administered in combination therapy with a chemotherapeutic drug selected from the group consisting of paclitaxel, docetaxel, doxorubicin, epirubicin, cyclophosphamide, capecitabine, tamoxifen, letrozole, carboplatin, gemcitabine, cisplatin, erlotinib, irinotecan, fluorouracil, and oxaliplatin. 
     
     
         32 . (canceled) 
     
     
         33 . The method of  claim 23 , wherein the pharmaceutical composition is administered in combination with radiation therapy. 
     
     
         34 . (canceled)