Immunogenic compositions and methods for treating neoplasia

Abstract

The invention provides immunogenic compositions comprising neoplastic cells expressing a cytokine (GM-CSF) formulated with at least one TLR agonist and methods of using the composition to induce or enhance an immune response.

1 . An immunogenic composition comprising one or more proliferation-incompetent genetically modified neoplastic cells expressing a recombinant immune stimulatory cytokine and comprising at least one Toll-like receptor (TLR) agonist. 
     
     
         2 .- 21 . (canceled) 
     
     
         22 . A method of inducing a neoplastic cell antigen-specific immune response in a subject having or having a propensity to develop a neoplasia, the method comprising administering to the subject an effective amount of an immunogenic composition comprising one or more proliferation-incompetent neoplastic cells expressing a recombinant immune stimulatory cytokine and comprising an exogenous Toll-like receptor (TLR) agonist in an amount sufficient to induce a neoplastic cell antigen-specific immune response in said subject. 
     
     
         23 . A method of treating or preventing a neoplasia in a subject having or having a propensity to develop a neoplasia, the method comprising administering to the subject an effective amount of the immunogenic composition of  claim 1  in an amount sufficient to induce a neoplastic cell antigen-specific immune response in said subject, thereby treating the subject. 
     
     
         24 . A method of treating or preventing tumor progression or metastasis in a subject having a neoplasia, the method comprising administering to the subject an effective amount of the immunogenic composition of  claim 1 , thereby treating or preventing tumor progression or metastasis in the subject. 
     
     
         25 . A method of treating an established tumor or preventing tumor formation in a subject, the method comprising administering to the subject an effective amount of the immunogenic composition of  claim 1 , thereby treating an established tumor or preventing tumor formation in the subject. 
     
     
         26 . A method of treating micrometastasis or residual disease in a subject having micrometastasis or residual disease, the method comprising administering to the subject an effective amount of the immunogenic composition of  claim 1 , thereby treating micrometastasis or residual disease in the subject. 
     
     
         27 . A method of immunizing a subject, the method comprising administering to the subject an immunogenic composition of  claim 1 . 
     
     
         28 . The method of  claim 22 , wherein the neoplastic cell is derived from a cancer cell line or is derived from a tumor. 
     
     
         29 . The method of  claim 28 , wherein the cancer cell line or tumor is selected from the group consisting of leukemia, chronic myeloid leukemia, prostate cancer, head and neck, Squamous Cell Carcinoma, tongue cancer, larynx cancer, tonsil cancer, hypopharynx cnacer, nasalpharynx cancer, breast cancer, colon cancer, lung cancer, melanoma, pancreatic cancer, glioblastoma and brain cancer. 
     
     
         30 . The method of  claim 22 , wherein the immunogenic composition is administered systemically or locally. 
     
     
         31 . The method of  claim 22 , wherein the immunogenic composition is administered by intramuscular injection, intravenous injection, intratumoral injection, or peritumoral injection 
     
     
         32 . The method of  claim 22 , further comprising administering to the subject an effective amount of one or more chemotherapeutics. 
     
     
         33 . The method of  claim 32 , wherein the one or more chemotherapeutics is selected from the group consisting of abiraterone acetate, altretamine, anhydrovinblastine, auristatin, bexarotene, bicalutamide, BMS 184476, 2,3,4,5,6-pentafluoro-N-(3-fluoro-4-methoxyphenyl)benzene sulfonamide, bleomycin, N,N-dimethyl-L-valyl-L-valyl-N-methyl-L-valyl-L-proly-1-Lproline-t-butylamide, cachectin, cemadotin, chlorambucil, cyclophosphamide, 3′,4′-didehydro-4′-deoxy-8′-norvin-caleukoblastine, docetaxol, doxetaxel, cyclophosphamide, carboplatin, carmustine (BCNU), cisplatin, cryptophycin, cyclophosphamide, cytarabine, dacarbazine (DTIC), dactinomycin, daunorubicin, decitabine dolastatin, doxorubicin (adriamycin), etoposide, 5-fluorouracil, finasteride, flutamide, hydroxyurea and hydroxyureataxanes, ifosfamide, liarozole, lonidamine, lomustine (CCNU), MDV3100, mechlorethamine (nitrogen mustard), melphalan, mivobulin isethionate, rhizoxin, sertenef, streptozocin, mitomycin, methotrexate, taxanes, nilutamide, onapristone, paclitaxel, prednimustine, procarbazine, RPR109881, stramustine phosphate, tamoxifen, tasonermin, taxol, tretinoin, vinblastine, vincristine, vindesine sulfate, and vinflunine. 
     
     
         34 . The method of  claim 22 , wherein the method enhances activation of dendritic cells and/or increases the number of AH1-specific cytotoxic T-cells or p15E-specific cytotoxic T-cells relative to the use of GVAX alone. 
     
     
         35 . The method of  claim 22 , wherein the method reduces or stabilizes tumor cell proliferation, tumor growth, or subject survival relative to the use of GVAX alone. 
     
     
         36 .- 41 . (canceled) 
     
     
         42 . A method of treating or preventing cervical cancer in a subject, the method comprising administering to the subject an effective amount of the immunogenic composition of  claim 1 , thereby treating or preventing cervical cancer in the subject. 
     
     
         43 . A method of treating polymorphic TLR deficiencies in a subject, the method comprising administering to the subject an effective amount of the immunogenic composition of  claim 1 , thereby treating the polymorphic TLR deficiencies in the subject.