Therapeutic and prophylactic methods using heat shock proteins

Abstract

The present invention relates to immunogenic complexes of heat shock proteins (hsp) noncovalently bound to exogenous antigenic molecules which when administered to an individual elicit specific immunological responses in the host. Methods of prevention and treatment of cancer and infectious disease are provided.

What is claimed is:  
     
         1 . A composition comprising an immunogenic amount of a complex of a heat shock protein noncovalently bound to an exogenous antigenic molecule.  
     
     
         2 . The composition of  claim 1  wherein the exogenous antigenic molecule is a cancer antigen or antigenic fragment or antigenic derivative thereof.  
     
     
         3 . The composition of  claim 1  wherein the exogenous antigenic molecule is an antigen of an infectious agent.  
     
     
         4 . The composition of  claim 1  wherein the exogenous antigenic molecule is an antigen of a virus or antigenic fragment or antigenic derivative thereof.  
     
     
         5 . The composition of  claim 1  wherein the exogenous antigenic molecule is an antigen of a bacterium or antigenic fragment or antigenic derivative thereof.  
     
     
         6 . The composition of  claim 1  wherein the exogenous antigenic molecule is an antigen of a fungus or antigenic fragment or antigenic derivative thereof.  
     
     
         7 . The composition of  claim 1  wherein the exogenous antigenic molecule is an antigen of a parasite or antigenic fragment or antigenic derivative thereof.  
     
     
         8 . The composition of  claim 1 ,  2 , or  3  wherein the heat shock protein is selected from the group consisting of hsp70, hsp90, gp96 and a combination thereof.  
     
     
         9 . The composition of  claim 1  wherein the heat shock protein is hsp70.  
     
     
         10 . The composition of  claim 1  wherein the heat shock protein is hsp 90.  
     
     
         11 . The composition of  claim 1  wherein the heat shock protein is gp96.  
     
     
         12 . The composition of  claim 4  wherein the virus is selected from the group consisting of hepatitis type B, hepatitis type C, influenza, varicella, adenovirus, herpes simplex type I (HSV-I), herpes simplex type II (HSV-II), rinderpest, rhinovirus, echovirus, rotavirus, respiratory synctial virus, papilloma virus, papova virus, cytomegalovirus, echinovirus, arbovirus, huntavirus, coxsachie virus, mumps virus, measles virus, rubella virus, polio virus, human immunodeficiency virus type I (HIV-I), and human immunodeficiency virus type II (HIV-II).  
     
     
         13 . The composition of  claim 5  wherein the bacterium is selected from the group consisting of mycobacterium, rickettsia, mycoplasma, neisseria and legionella.  
     
     
         14 . The composition of  claim 1  wherein the exogenous antigenic molecule is an antigen of a protozoa or antigenic fragment or antigenic derivative thereof.  
     
     
         15 . The composition of  claim 14  wherein the protozoa is selected from the group consisting of leishmania, kokzidioa, and trypanosoma.  
     
     
         16 . The composition of  claim 7  wherein the parasite is selected from the group consisting of chlamydia and rickettsia.  
     
     
         17 . The composition of  claim 2  wherein the cancer is selected from the group consisting of fibrosarcoma, myxosarcoma, liposarcoma, chondrosarcoma, osteogenic sarcoma, chordoma, angiosarcoma, endotheliosarcoma, lymphangiosarcoma, lymphangioendotheliosarcoma, synovioma, mesothelioma, Ewing's tumor, leiomyosarcoma, rhabdomyosarcoma, colon carcinoma, pancreatic cancer, breast cancer, ovarian cancer, prostate cancer, squamous cell carcinoma, basal cell carcinoma, adenocarcinoma, sweat gland carcinoma, sebaceous gland carcinoma, papillary carcinoma, papillary adenocarcinomas, cystadenocarcinoma, medullary carcinoma, bronchogenic S carcinoma, renal cell carcinoma, hepatoma, bile duct carcinoma, choriocarcinoma, seminoma, embryonal carcinoma, Wilms' tumor, cervical cancer, testicular tumor, lung carcinoma, small cell lung carcinoma, bladder carcinoma, epithelial carcinoma, glioma, astrocytoma, medulloblastoma, craniopharyngioma, ependymoma, pinealoma, hemangioblastoma, acoustic neuroma, oligodendroglioma, meningioma, melanoma, neuroblastoma, retinoblastoma, leukemia, lymphoma, multiple myeloma, Waldenström's macroglobulinemia, and heavy chain disease.  
     
     
         18 . The composition of  claim 1  further comprising a pharmaceutically acceptable carrier.  
     
     
         19 . The composition of  claim 1  further comprising a cytokine.  
     
     
         20 . The composition of  claim 19  wherein the cytokine is selected from the group consisting of interferon-α, interferon-γ, interleukin-2, interleukin-4, interleukin-6, and tumor necrosis factor.  
     
     
         21 . A method of eliciting an immune response in an individual comprising administering to the individual a complex of a heat shock protein noncovalently bound to an exogenous antigenic molecule.  
     
     
         22 . The method according to  claim 21  wherein the exogenous antigenic molecule is selected from the group consisting of a cancer antigen, an antigen of an infectious agent, and an antigenic fragment or antigenic derivative of a cancer antigen or antigen of an infectious agent.  
     
     
         23 . A method of treating an individual having cancer comprising administering to the individual a complex of a heat shock protein noncovalently bound to an exogenous antigenic molecule.  
     
     
         24 . The method according to  claim 23  wherein the exogenous antigenic molecule is a cancer antigen or antigenic fragment or antigenic derivative thereof.  
     
     
         25 . The method according to  claim 23  wherein the exogenous antigenic molecule is a tumor-specific antigen or antigenic fragment or antigenic derivative thereof.  
     
     
         26 . The method according to  claim 24  wherein the cancer is selected from the group consisting of fibrosarcoma, myxosarcoma, liposarcoma, chondrosarcoma, osteogenic sarcoma, chordoma, angiosarcoma, endotheliosarcoma, lymphangiosarcoma, lymphangioendotheliosarcoma, synovioma, mesothelioma, Ewing's tumor, leiomyosarcoma, rhabdomyosarcoma, colon carcinoma, pancreatic cancer, breast cancer, ovarian cancer, prostate cancer, squamous cell carcinoma, basal cell carcinoma, adenocarcinoma, sweat gland carcinoma, sebaceous gland carcinoma, papillary carcinoma, papillary adenocarcinomas, cystadenocarcinoma, medullary carcinoma, bronchogenic carcinoma, renal cell carcinoma, hepatoma, bile duct carcinoma, choriocarcinoma, seminoma, embryonal carcinoma, Wilius' tumor, cervical cancer, testicular tumor, lung carcinoma, small cell lung carcinoma, bladder carcinoma, epithelial carcinoma, glioma, astrocytoma, medulloblastoma, craniopharyngioma, ependymoma, pinealoma, hemangioblastoma, acoustic neuroma, oligodendroglioma, meningioma, melanoma, neuroblastoma, retinoblastoma, leukemia, lymphoma, multiple myeloma, Waldenström's macroglobulinemia, and heavy chain disease.  
     
     
         27 . The method according to  claim 21  or  23  wherein the heat shock protein is selected from the group consisting of hsp70, hsp90, gp96 and a combination thereof.  
     
     
         28 . The method according to  claim 21  or  23  wherein the heat shock protein is hsp70.  
     
     
         29 . The method according to  claim 21  or  23  wherein the heat shock protein is hsp90.  
     
     
         30 . The method according to  claim 21  or  23  wherein the heat shock protein is gp96.  
     
     
         31 . A method of preventing cancer in an individual in whom prevention of cancer is desired comprising administering to the individual a complex of a heat shock protein noncovalently bound to an exogenous antigenic molecule.  
     
     
         32 . The method according to  claim 31  wherein the exogenous antigenic molecule is a cancer antigen or antigenic fragment or antigenic derivative thereof.  
     
     
         33 . The method according to  claim 31  wherein the heat shock protein is selected from the group consisting of hsp70, hsp90, gp96 and a combination thereof.  
     
     
         34 . A method of treating or preventing infectious disease in an individual in whom such treatment or prevention is desired comprising administering to the individual a complex of a heat shock protein noncovalently bound to an exogenous antigenic molecule.  
     
     
         35 . The method according to  claim 34  wherein the exogenous antigenic molecule is an antigen of an infectious agent.  
     
     
         36 . The method according to  claim 35  wherein the infectious agent is a virus, bacterium, fungus, parasite, or protozoa.  
     
     
         37 . The method according to  claim 35  wherein the heat shock protein is selected from the group consisting of hsp70, hsp90, gp96, and a combination thereof.  
     
     
         38 . The method according to  claim 21 ,  23 ,  31 , or  34  wherein the individual is a human.  
     
     
         39 . A kit comprising in a container a purified complex of a heat shock protein noncovalently bound to an exogenous antigenic molecule, in a pharmaceutically acceptable carrier.  
     
     
         40 . The kit of  claim 39  wherein the exogenous antigenic molecule is a cancer antigen.  
     
     
         41 . The kit of  claim 39  wherein the exogenous antigenic molecule is an antigen of an infectious agent.  
     
     
         42 . The kit of  claim 41  wherein the infectious agent is a virus, bacterium, fungus, parasite, or protozoa.