Kits comprising heat shock protein-antigenic molecule complexes

Abstract

The present invention relates to methods and compositions for eliciting an immune response and the prevention-and treatment of primary and metastatic neoplastic diseases and infectious diseases. The methods of the invention comprise administering a composition comprising an effective amount of a complex, in which the complex consists essentially of a heat shock protein (hsp) noncovalently bound to an antigenic molecule. Optionally, the methods further comprise administering antigen presenting cells sensitized with complexes of hsps noncovalently bound to an antigenic molecule. “Antigenic molecule” as used herein refers to the peptides with which the hsps are endogenously associated in vivo as well as exogenous antigens/immunogens (i.e., with which the hsps are not complexed in vivo) or antigenic/immunogenic fragments and derivatives thereof. In a preferred embodiment, the complex is autologous to the individual. In a specific embodiment, the effective amounts of the complex are in the range of 0.1 to 9.0 micrograms for complexes comprising hsp70, 5 to 49 micrograms for hsp90, and 0.1 to 9.0 micrograms for gp96.

What is claimed is:  
     
         1 . A method of eliciting an immune response in a human individual comprising administering to the individual a first composition comprising an amount of a first complex of less than 10 micrograms effective to elicit an immune response, said first complex consisting essentially of a heat shock protein (hsp) 70 noncovalently bound to a first antigenic molecule.  
     
     
         2 . A method of eliciting an immune response in a human individual comprising administering to the individual a first composition comprising an amount of a first complex of less than 50 micrograms effective to elicit an immune response, said first complex consisting essentially of an hsp90 noncovalently bound to a first antigenic molecule.  
     
     
         3 . A method of eliciting an immune response in a human individual comprising administering to the individual a first composition comprising an amount of a first complex of less than 10 micrograms effective to elicit an immune response, said first complex consisting essentially of a gp96 noncovalently bound to a first antigenic molecule.  
     
     
         4 . The method according to claims  1 ,  2  or  3  in which the individual has liver cancer, colon cancer, or breast cancer.  
     
     
         5 . The method according to  claim 1  in which the amount of the first complex is in the range of 0.1 to 9.0 micrograms.  
     
     
         6 . The method according to  claim 2  in which the amount of the first complex is in the range of 5 to 49 micrograms.  
     
     
         7 . The method according to  claim 3  in which the amount of the first complex is in the range of 0.1 to 9.0 micrograms.  
     
     
         8 . The method according to  claim 1  in which the amount of the first complex is in the range of 0.5 to 2.0 micrograms.  
     
     
         9 . The method according to  claim 2  in which the amount of the first complex is in the range of 5 to 40 micrograms.  
     
     
         10 . The method according to  claim 3  in which the amount of the first complex is in the range of 0.5 to 2.0 micrograms.  
     
     
         11 . The method according to  claim 1 ,  2  or  3 , further comprising administering to the individual an effective amount of a biological response modifier selected from the group consisting of interferon-α, interferon-γ, interleukin-2, interleukin-4, interleukin-6, and tumor necrosis factor.  
     
     
         12 . The method according to  claim 1 ,  2  or  3  in which said administering step is repeated at weekly intervals.  
     
     
         13 . The method according to  claim 1 ,  2  or  3  in which said first complex is administered intradermally.  
     
     
         14 . The method according to  claim 1 ,  2  or  3  in which said first complex is administered mucosally.  
     
     
         15 . The method according to  claim 1 ,  2  or  3  in which said administering step is repeated five times, the first administration being on the left arm, the second administration being on the right arm, the third administration being on the left belly, the fourth administration being on the right belly, the fifth administration being on the left thigh, and the sixth administration being on the right thigh; said first through sixth administration being intradermally.  
     
     
         16 . A method of treating a human individual having cancer, comprising administering to the individual a first-composition comprising a therapeutically effective amount of a first complex of less than 10 micrograms, said first complex consisting essentially of an hsp70 noncovalently bound to a first antigenic molecule.  
     
     
         17 . A method of treating a human individual having cancer, comprising administering to the individual a first composition comprising a therapeutically effective amount of a first complex of less than 50 micrograms, said first complex consisting essentially of an hsp90 noncovalently bound to a first antigenic molecule.  
     
     
         18 . A method of treating a human individual having cancer, comprising administering to the individual a first composition comprising a therapeutically effective amount of a first complex of less than 10 micrograms, said first complex consisting essentially of a gp96 noncovalently bound to a first antigenic molecule.  
     
     
         19 . The method according to  claim 16 ,  17  or  18  in which the cancer comprises a sarcoma or carcinoma, 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, 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.  
     
     
         20 . The method according to  claim 16  in which the amount of the first complex is in the range of 0.1 to 9.0 micrograms.  
     
     
         21 . The method according to  claim 17  in which the amount of the first complex is in the range of 5 to 49 micrograms.  
     
     
         22 . The method according to  claim 18  in which the amount of the first complex is in the range of 0.1 to 9.0 micrograms.  
     
     
         23 . The method according to  claim 16  in which the amount of the first complex is in the range of 0.5 to 2.0 micrograms.  
     
     
         24 . The method according to  claim 17  in which the amount of the first complex is in the range of 5 to 40 micrograms.  
     
     
         25 . The method according to  claim 18  in which the amount of the first complex is in the range of 0.5 to 2.0 micrograms.  
     
     
         26 . The method according to  claim 16 ,  17  or  18  in which the first antigenic molecule is a peptide with which the hsp is endogenously associated in vivo, and the first complex is prepared from cancerous tissue autologous to the individual.  
     
     
         27 . The method according to  claim 16 ,  17  or  18  in which the first antigenic molecule is a peptide with which the hsp is endogenously associated in vivo, and the first complex is prepared from cancerous tissue allogeneic to the individual.  
     
     
         28 . The method according to  claim 16 ,  17 , or  18  in which the first antigenic molecule is a peptide with which the hsp is endogenously associated in vivo, and the first complex is prepared from cancerous tissue.  
     
     
         29 . The method according to  claim 28  in which the cancerous tissue is from the individual.  
     
     
         30 . The method according to  claim 16 ,  17 , or  18  in which the first complex of the hsp and first antigenic molecule is produced in vitro.  
     
     
         31 . The method according to  claim 30  in which the first antigenic molecule is a tumor-specific antigen.  
     
     
         32 . The method according to  claim 16 ,  17  or  18 , further comprising administering to the individual an effective amount of a biological response modifier selected from the group consisting of interferon-α, interferon-γ, interleukin-2, interleukin-4, interleukin-6, and tumor necrosis factor.  
     
     
         33 . The method according to  claim 16 ,  17  or  18  in which said administering step is repeated at weekly intervals.  
     
     
         34 . The method according to  claim 16 ,  17  or  18  in which the first complex is purified to 60 to 100 percent of total mg protein.  
     
     
         35 . The method according to  claim 16 ,  17  or  18  in which the first complex is administered intradermally.  
     
     
         36 . The method according to  claim 16 ,  17  or  18  in which the first complex is administered mucosally.  
     
     
         37 . The method according to  claim 23 ,  24  or  25  in which said administering step is repeated five times, the first administration being on the left arm, the second administration being on the right arm, the third administration being on the left belly, the fourth administration being on the right belly, the fifth administration being on the left thigh, and the sixth administration being on the right thigh; said first through sixth administration being intradermally.  
     
     
         38 . A method of treating a human individual having cancer comprising: 
 (a) administering to the individual a composition comprising about 2 micrograms of a complex, said complex consisting essentially of a gp96 noncovalently bound to a peptide, said complex having been isolated from cancerous tissue of said individual; and    (b) repeating said administering of step (a) at weekly intervals for five weeks, the first administration being on the left arm, the second administration being on the right arm, the third administration being on the left belly, the fourth administration being on the right belly, the fifth administration being on the left thigh, and the sixth administration being on the right thigh; said first through sixth administration being intradermally.    
     
     
         39 . A method of preventing cancer in a human individual in whom prevention of cancer is desired comprising administering to the individual a first composition comprising an amount of a first complex of less than 10 micrograms effective to inhibit cancer, said first complex consisting essentially of an hsp70 noncovalently bound to a first antigenic molecule.  
     
     
         40 . A method of preventing cancer in a human individual in whom prevention of cancer is desired, comprising administering to the individual a first composition comprising an amount of a first complex of less than 50 micrograms effective to inhibit cancer, said first complex consisting essentially of an hsp90 noncovalently bound to a first antigenic molecule.  
     
     
         41 . A method of preventing cancer in a human individual in whom prevention of cancer is desired, comprising administering to the individual a first composition comprising an amount of a first complex of less than 10 micrograms effective to inhibit cancer, said first complex consisting essentially of a gp96 noncovalently bound to a first antigenic molecule.  
     
     
         42 . The method according to  claim 39 , in which the amount of the first complex is in the range of 0.1 to 9.0 micrograms.  
     
     
         43 . The method according to  claim 40 , in which the amount of the first complex is in the range of 5 to 49 micrograms.  
     
     
         44 . The method according to  claim 41 , in which the amount of the first complex is in the range of 0.1 to 9.0 micrograms.  
     
     
         45 . The method according to  claim 39 , in which the amount of the first complex is in the range of 0.5 to 2.0 micrograms.  
     
     
         46 . The method according to  claim 40 , in which the amount of the first complex is in the range of 5 to 40 micrograms.  
     
     
         47 . The method according to  claim 41 , in which the amount of the first complex is in the range of 0.5 to 2.0 micrograms.  
     
     
         48 . The method according to  claim 39 ,  40  or  41  in which the first antigenic molecule is a peptide with which the hsp is endogenously associated in vivo.  
     
     
         49 . The method according to  claim 48  in which the first complex is prepared from cancerous tissue.  
     
     
         50 . The method according to  claim 39 ,  40  or  41  in which the first complex of the hsp and first antigenic molecule is produced in vitro.  
     
     
         51 . The method according to  claim 50  in which the first antigenic molecule is a tumor-specific antigen.  
     
     
         52 . A method of treating or preventing an infectious disease in a human individual in whom such treatment or prevention is desired comprising administering to the individual a first composition comprising an amount of a first complex of less than 10 micrograms effective to treat or prevent infectious disease, said first complex consisting essentially of an hsp70 noncovalently bound to a first antigenic molecule.  
     
     
         53 . A method of treating or preventing an infectious disease in a human individual in whom such treatment or prevention is desired comprising administering to the individual a first composition comprising an amount of a first complex of less than 50 micrograms effective to treat or prevent infectious disease, said first complex consisting essentially of an hsp90 noncovalently bound to a first antigenic molecule.  
     
     
         54 . A method of treating or preventing an infectious disease in a human individual in whom such treatment or prevention is desired comprising administering to the individual a first composition comprising an amount of a first complex of less than 10 micrograms effective to treat or prevent infectious disease, said first complex consisting essentially of a gp96 noncovalently bound to a first antigenic molecule.  
     
     
         55 . The method according to  claim 52  in which the amount of the first complex is in the range of 0.1 to 9.0 micrograms.  
     
     
         56 . The method according to  claim 53  in which the amount of the first complex is in the range of 5 to 49 micrograms.  
     
     
         57 . The method according to  claim 54  in which the amount of the first complex is in the range of 0.1 to 9.0 micrograms.  
     
     
         58 . The method according to  claim 52  in which the amount of the first complex is in the range of 0.5 to 2.0 micrograms.  
     
     
         59 . The method according to  claim 53  in which the amount of the first complex is in the range of 5 to 40 micrograms.  
     
     
         60 . The method according to  claim 54  in which the amount of the first complex is in the range of 0.5 to 2.0 micrograms.  
     
     
         61 . The method according to  claim 52 ,  53  or  54  in which the first antigenic molecule is a peptide with which the hsp is endogenously associated in cells infected with an infectious agent that causes the infectious disease.  
     
     
         62 . The method according to  claim 52 ,  53  or  54  in which the first antigenic molecule is an antigen of an infectious agent that causes the infectious disease.  
     
     
         63 . The method according to  claim 62  in which the infectious agent is a virus, bacterium, protozoa, fungus, or parasite.  
     
     
         64 . The method according to  claim 1  which further comprises administering to the individual a second composition comprising antigen presenting cells sensitized in vitro with a sensitizing amount of a second complex of a second hsp noncovalently bound to a second antigenic molecule in which said sensitized antigen presenting cells are administered before, concurrently or after administration of the first composition.  
     
     
         65 . The method according to  claim 2  which further comprises administering to the individual a second composition comprising antigen presenting cells sensitized in vitro with a sensitizing amount of a second complex of a second hsp noncovalently bound to a second antigenic molecule in which said sensitized antigen presenting cells are administered before, concurrently or after administration of the first composition.  
     
     
         66 . The method according to  claim 3  which further comprises administering to the individual a second composition comprising antigen presenting cells sensitized in vitro with a sensitizing amount of a second complex of a second hsp noncovalently bound to a second antigenic molecule in which said sensitized antigen presenting cells are administered before, concurrently or after administration of the first composition.  
     
     
         67 . The method according to  claim 64 ,  65  or  66  in which said second hsp is selected from the group consisting of hsp70, hsp90, gp96, and combinations of the foregoing.  
     
     
         68 . The method according to  claim 64 ,  65  or  66  in which the first and second complexes are the same.  
     
     
         69 . The method according to  claim 64 ,  65  or  66  in which the individual has liver cancer, colon cancer, or breast cancer.  
     
     
         70 . The method according to  claim 64  in which the amount of the first complex is in the range of 0.1 to 9.0 micrograms.  
     
     
         71 . The method according to  claim 65  in which the amount of the first complex is in the range of 5 to 49 micrograms.  
     
     
         72 . The method according to  claim 66  in which the amount of the first complex is in the range of 0.1 to 9.0 micrograms.  
     
     
         73 . The method according to  claim 64  in which the amount of the first complex is in the range of 0.5 to 2.0 micrograms.  
     
     
         74 . The method according to  claim 65  in which the amount of the first complex is in the range of 5 to 40 micrograms.  
     
     
         75 . The method according to  claim 66  in which the amount of the first complex is in the range of 0.5 to 2.0 micrograms.  
     
     
         76 . The method according to  claim 64 ,  65  or  66  further comprising administering to the individual an effective amount of a biological response modifier selected from the group consisting of interferon-α, interferon-γ, interleukin-2, interleukin-4, interleukin-6, and-tumor necrosis factor.  
     
     
         77 . The method according to  claim 64 ,  65  or  66  in which administering the first composition is repeated at weekly intervals.  
     
     
         78 . The method according to  claim 64 ,  65  or  66  in which administering the second composition is repeated at weekly intervals.  
     
     
         79 . The method according to  claim 64 ,  65  or  66  in which the first complex is administered intradermally.  
     
     
         80 . The method according to  claim 64 ,  65  or  66  in which the first complex is administered mucosally.  
     
     
         81 . The method according to  claim 64 ,  65  or  66  in which the sensitized antigen presenting cells are administered intravenously.  
     
     
         82 . The method according to  claim 64 ,  65  or  66  in which 10 6  to 10 12  antigen presenting cells are administered.  
     
     
         83 . The method according to  claim 16  which further comprises administering to the individual a second composition comprising antigen presenting cells sensitized in vitro with a sensitizing amount of a second complex of a second hsp noncovalently bound to a second antigenic molecule in which said sensitized antigen presenting cells are administered before, concurrently or after administration of the first complex.  
     
     
         84 . The method according to  claim 17  which further comprises administering to the individual a second composition comprising antigen presenting cells sensitized in vitro with a sensitizing amount of a second complex of a second hsp noncovalently bound to a second antigenic molecule in which said sensitized antigen presenting cells are administered before, concurrently or after administration of the first complex.  
     
     
         85 . The method according to  claim 18  which further comprises administering to the individual a second composition comprising antigen presenting cells sensitized in vitro with a sensitizing amount of a second complex of a second hsp noncovalently bound to a second antigenic molecule in which said sensitized antigen presenting cells are administered before, concurrently or after administration of the first complex.  
     
     
         86 . The method according to  claim 83 ,  84  or  85  in which said second hsp is selected from the group consisting of hsp70, hsp90, gp96, and combination of the foregoing.  
     
     
         87 . The method according to  claim 83 ,  84  or  85  in which the first and second complexes are the same  
     
     
         88 . The method according to  claim 83 ,  84  or  85  in which the cancer comprises a sarcoma or carcinoma, 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, 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.  
     
     
         89 . The method according to  claim 83  in which the amount of the first complex is in the range of 0.1 to 9.0 micrograms.  
     
     
         90 . The method according to  claim 84  in which the amount of the first complex is in the range of 5 to 49 micrograms.  
     
     
         91 . The method according to  claim 85  in which the amount of the first complex is in the range of 0.1 to 9.0 micrograms.  
     
     
         92 . The method according to  claim 83  in which the amount of the first complex is in the range of 0.5 to 2.0 micrograms.  
     
     
         93 . The method according to  claim 84  in which the amount of the first complex is in the range of 5 to 40 micrograms.  
     
     
         94 . The method according to  claim 85  in which the amount of the first complex is in the range of 0.5 to 2.0 micrograms.  
     
     
         95 . The method according to  claim 83 ,  84  or  85  in which said second antigenic molecule is a peptide with which said second heat shock protein is endogenously associated in vivo, and said second complex is prepared from cancerous tissue autologous to the individual.  
     
     
         96 . The method according to  claim 83 ,  84  or  85  in which said second antigenic molecule is a peptide with which said second heat shock protein is endogenously associated in vivo, and said second complex is prepared from cancerous tissue allogeneic to the individual.  
     
     
         97 . The method according to  claim 83 ,  84  or  85  in which said second antigenic molecule is a peptide with which said second heat shock protein is endogenously associated in vivo, and said second complex is prepared from cancerous tissue.  
     
     
         98 . The method according to  claim 97  in which the cancerous tissue is from the individual.  
     
     
         99 . The method according to  claim 83 ,  84  or  85  in which the second complex of the second hsp and second antigenic molecule is produced in vitro.  
     
     
         100 . The method according to  claim 99  in which the second antigenic molecule is a tumor-specific antigen.  
     
     
         101 . The method according to  claim 83 ,  84  or  85  further comprising administering to the individual an effective amount of a biological response modifier selected from the group consisting of interferon-α, interferon-γ, interleukin-2, interleukin-4, interleukin-6, and tumor necrosis factor.  
     
     
         102 . The method according to  claim 83 ,  84  or  85  in which administering the first composition is repeated at weekly intervals.  
     
     
         103 . The method according to  claim 83 ,  84  or  85  in which administering the second composition is repeated at weekly intervals.  
     
     
         104 . The method according to  claim 83 ,  84  or  85  in which the first complex is administered intradermally.  
     
     
         105 . The method according to  claim 83 ,  84  or  85  in which the first complex is administered mucosally.  
     
     
         106 . The method according to  claim 83 ,  84  or  85  in which the sensitized antigen presenting cells are administered intravenously.  
     
     
         107 . The method according to  claim 83 ,  84  or  85  in which 10 6  to 10 12  antigen presenting cells are administered.  
     
     
         108 . The method according to  claim 39  which further comprises administering to the individual a second composition comprising antigen presenting cells sensitized in vitro with a sensitizing amount of a second complex of a second hsp noncovalently bound to a second antigenic molecule in which said sensitized antigen presenting cells are administered before, concurrently or after administration of the first complex.  
     
     
         109 . The method according to  claim 40  which further comprises administering to the individual a second composition comprising antigen presenting cells sensitized in vitro with a sensitizing amount of a second complex of a second hsp noncovalently bound to a second antigenic molecule in which said sensitized antigen presenting cells are administered before, concurrently or after administration of the first complex.  
     
     
         110 . The method according to  claim 41  which further comprises administering to the individual a second composition comprising antigen presenting cells sensitized in vitro with a sensitizing amount of a second complex of a second hsp noncovalently bound to a second antigenic molecule in which said sensitized antigen presenting cells are administered before, concurrently or after administration of the first complex.  
     
     
         111 . The method according to  claim 108 ,  109  or  110  in which said second hsp is selected from the group consisting of hsp70, hsp90, gp96 and combinations of the foregoing.  
     
     
         112 . The method according to  claim 108 ,  109  or  110  in which the first and second complexes are the same.  
     
     
         113 . The method according to  claim 108  in which the amount of the first complex is in the range of 0.1 to 9.0 micrograms.  
     
     
         114 . The method according to  claim 109  in which the amount of the first complex is in the range of 5 to 49 micrograms.  
     
     
         115 . The method according to  claim 110  in which the amount of the first complex is in the range of 0.1 to 9.0 micrograms.  
     
     
         116 . The method according to  claim 108  in which the amount of the first complex is in the range of 0.5 to 2.0 micrograms.  
     
     
         117 . The method according to  claim 109  in which the amount of the first complex is in the range of 5 to 40 micrograms.  
     
     
         118 . The method according to  claim 110  in which the amount of the first complex is in the range of 0.5 to 2.0 micrograms.  
     
     
         119 . The method according to  claim 108 ,  109  or  110  in which said second antigenic molecule is a peptide with which said second heat shock protein is endogenously associated in vivo.  
     
     
         120 . The method according to  claim 52  which further comprises administering to the individual a second composition comprising antigen presenting cells sensitized in vitro with a sensitizing amount of a second complex of a second hsp noncovalently bound to a second antigenic molecule in which said sensitized antigen presenting cells are administered before, concurrently or after administration of the first complex.  
     
     
         121 . The method according to  claim 53  which further comprises administering to the individual a second composition comprising antigen presenting cells sensitized in vitro with a sensitizing amount of a second complex of a second hsp noncovalently bound to a second antigenic molecule in which said sensitized antigen presenting cells are administered before, concurrently or after administration of the first complex.  
     
     
         122 . The method according to  claim 54  which further comprises administering to the individual a second composition comprising antigen presenting cells sensitized in vitro with a sensitizing amount of a second complex of a second hsp noncovalently bound to a second antigenic molecule in which said sensitized antigen presenting cells are administered before, concurrently or after administration of the first complex.  
     
     
         123 . The method according to  claim 120 ,  121  or  122  in which said second hsp is selected from the group consisting of hsp70, hsp90, gp96 and combinations of the foregoing.  
     
     
         124 . The method according to  claim 120 ,  121  or  122  in which the first and second complexes are the same.  
     
     
         125 . The method according to  claim 120  in which the amount of the first complex is in the range of 0.1 to 9.0 micrograms.  
     
     
         126 . The method according to  claim 121  in which the amount of the first complex is in the range of 5 to 49 micrograms.  
     
     
         127 . The method according to  claim 122  in which the amount of the first complex is in the range of 0.1 to 9.0 micrograms.  
     
     
         128 . The method according to  claim 120  in which the amount of the first complex is in the range of 0.5 to 2.0 micrograms.  
     
     
         129 . The method according to  claim 121  in which the amount of the first complex is in the range of 5 to 40 micrograms.  
     
     
         130 . The method according to  claim 122  in which the amount of the first complex is in the range of 0.5 to 2.0 micrograms.  
     
     
         131 . The method according to  claim 120 ,  121  or  122  in which said second antigenic molecule is a peptide with which said second heat shock protein is endogenously associated in cells infected with an infectious agent that causes the infectious disease.  
     
     
         132 . The method according to  claim 120 ,  121  or  122  in which said second antigenic molecule is an antigen of an infectious agent that causes the infectious disease.  
     
     
         133 . The method according to  claim 132  in which the infectious agent is a virus, bacterium, protozoa, fungus, or parasite.  
     
     
         134 . The method according to  claim 64 ,  65  or  66  in which the antigen presenting cells comprise macrophages.  
     
     
         135 . The method according to  claim 83 ,  84  or  85  in which the antigen presenting cells comprise macrophages.  
     
     
         136 . The method according to  claim 108 ,  109  or  110  in which the antigen presenting cells comprise macrophages.  
     
     
         137 . The method according to  claim 120 ,  121  or  122  in which the antigen presenting cells comprise macrophages.  
     
     
         138 . A kit comprising in a container a composition comprising an amount of a complex of less than 10 micrograms effective to induce an immune response or treat or prevent cancer or infectious disease in a mammal, said complex consisting essentially of an hsp70 noncovalently bound to an antigenic molecule.  
     
     
         139 . The kit of  claim 138  which further comprises in a second container human antigen presenting cells.  
     
     
         140 . A kit comprising in a container a composition comprising an amount of a complex of less than 50 micrograms effective to induce an immune response or treat or prevent cancer or infectious disease in a mammal, said complex consisting essentially of an hsp9o noncovalently bound to an antigenic molecule.  
     
     
         141 . The kit of  claim 140  which further comprises in a second container human antigen presenting cells.  
     
     
         142 . A kit comprising in a container a composition comprising an amount of a complex of less than 10 micrograms effective to induce an immune response or treat or prevent cancer or infectious disease in a mammal, said complex consisting essentially of a gp96 noncovalently bound to an antigenic molecule.  
     
     
         143 . The kit of  claim 142  which further comprises in a second container human antigen presenting cells.  
     
     
         144 . A kit comprising a plurality of containers, each container having a composition comprising an amount of a complex of less than 10 micrograms effective to induce an immune response or treat or prevent cancer or infectious disease, said complex consisting essentially of an hsp70 noncovalently bound to an antigenic molecule.  
     
     
         145 . The kit of  claim 138  in which the amount of the complex is in the range of 0.1 to 9.0 micrograms.  
     
     
         146 . The kit of  claim 138  in which the amount of the complex is in the range of 0.5 to 2.0 micrograms.  
     
     
         147 . The kit of  claim 145  which further comprises in a second container human antigen presenting cells.  
     
     
         148 . The kit of  claim 146  which further comprises in a second container human antigen presenting cells.  
     
     
         149 . The kit of  claim 140  in which the amount of the complex is in the range of 5 to 49 micrograms.  
     
     
         150 . The kit of  claim 140  in which the amount of the complex is in the range of 5 to 40 micrograms.  
     
     
         151 . The kit of  claim 149  which further comprises in a second container human antigen presenting cells.  
     
     
         152 . The kit of  claim 150  which further comprises in a second container human antigen presenting cells.  
     
     
         153 . The kit of  claim 142  in which the amount of the complex is in the range of 0.1 to 9.0 micrograms.  
     
     
         154 . The kit of  claim 142  in which the amount of the complex is in the range of 0.5 to 2.0 micrograms.  
     
     
         155 . The kit of  claim 153  which further comprises in a second container human antigen presenting cells.  
     
     
         156 . The kit of  claim 154  which further comprises in a second container human antigen presenting cells.  
     
     
         157 . The method according to  claim 1 ,  2 , or  3  in which the first complex is purified to apparent homogeneity as detected by sodium dodecyl sulfate-polyacrylamide gel electrophoresis.  
     
     
         158 . A pharmaceutical composition comprising an amount of a complex of less than 10 micrograms effective to induce an immune response or treat or prevent cancer or infectious disease in a mammal, said complex consisting essentially of an hsp70 noncovalently bound to an antigenic molecule; and a pharmaceutically acceptable carrier.  
     
     
         159 . A pharmaceutical composition comprising an amount of a complex of less than 50 micrograms effective to induce an immune response or treat or prevent cancer or infectious disease in a mammal, said complex consisting essentially of an hsp90 noncovalently bound to an antigenic molecule; and a pharmaceutically acceptable carrier.  
     
     
         160 . A pharmaceutical composition comprising an amount of a complex of less than 10 micrograms effective to induce an immune response or treat or prevent cancer or infectious disease in a mammal, said complex consisting essentially of an gp96 noncovalently bound to an antigenic molecule; and a pharmaceutically acceptable carrier.