Abstract: The 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. “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. The effective amounts of the complex are in the range of 10-600 micrograms for complexes comprising hsp70, 50-1000 micrograms for hsp90, and 10-600 micrograms for gp96.

Abstract: The present invention is directed to a method of inhibiting tumor cell growth. Tumor cells from a pateint are recombinantly engineered to express the B7 surface protein and these cells are then readminsistered to the pateint. The presence of the B7 molecule on the tumor cell surface stimulates a broad immunologic response against both the B7-transfected and non-transfected tumor cells and results in the immunologic killing of localized and metastatic tumor cells. B7 transfection of the tumor cells, or cell membranes, serves as a stimulant to engender a potent immunologic response against the surface antigens present on the tumor cells.

Abstract: Treatment of solid tumors, including their metastases, without radiation, surgery or standard chemotherapeutic agents is described. Ex vivo stimulation of cells, selection of specific V&bgr; subsets of stimulated cells and reinfusion of the V&bgr; subsets of stimulated cells is employed for cancer therapy.

Abstract: The present invention is generally directed to the identification of mouse and human genes that inhibit the growth of a tumor and induce apoptosis in cancer cells, and to polypeptides encoded by such genes. In particular, the invention concerns the nucleotide sequence of one such tumor-inhibiting gene, tag7, and the amino acid sequence of a polypeptide encoded by tag7. The invention also provides isolated nucleic acid molecules comprising tag7 polynucleotides, and vectors and host cells comprising these isolated nucleic acid molecules. The invention also provides methods of producing tag7 polypeptides using these nucleic acid molecules, vectors and host cells, tag7 polypeptides made by these methods and antibodies that specifically bind to the tag7 polypeptide. The invention also concerns methods of inhibiting tumor growth and inducing tumor cell apoptosis, and methods of cancer therapy, using the present tag7 nucleic acid molecules and polypeptides.

Abstract: The present invention relates to compositions comprising a population of non-covalent heat shock protein 70-peptide complexes purified from mammalian tumor tissues or mammalian cells infected with an infectious agent. When administered to a mammal, the compositions are capable of eliciting an immune response. The compositions are also useful for treatment of cancer and infectious diseases in animals.

Abstract: A method is provided for treating a Th1 mediated disease state by administration to a subject of a slow release vehicle such as a liposome or microsphere formulation containing an antigenic peptide and a Th1 specific immunomodulator wherein the antigenic peptide contains a T cell epitope and is released from the vehicle at a rate in the range from about 10 to 2 weight percent of the peptide in 24 hours at 37° C.

Abstract: A method of inhibiting growth of tumor cells which overexpress a growth factor receptor or growth factor by treatment of the cells with antibodies which inhibit the growth factor receptor function, is disclosed. A method of treating tumor cells with antibodies which inhibit growth factor receptor function, and with cytotoxic factor(s) such as tumor necrosis factor, is also disclosed. By inhibiting growth factor receptor functions tumor cells are rendered more susceptible to cytotoxic factors.

Abstract: We have discovered that by using a recombinant viral vector, preferably a pox virus vector having at least one insertion site containing a DNA segment encoding prostate-specific antigen (PSA), operably linked to a promoter capable of expression in the host, a specific humoral and cellular immune response to PSA can be generated. The method preferably comprises introducing a sufficient amount of the recombinant pox virus vector into a host to stimulate the immune response, and contacting the host with additional PSA at periodic intervals thereafter. The additional PSA may be added by using a second pox virus vector from a different pox genus. In another embodiment, additional PSA can be added by contacting the host with PSA by a variety of other methods, including in one preferred embodiment adding PSA. The PSA may be formulated with an adjuvant or in a liposomal formulation.

Abstract: Identification of defective ER and subclassifying ER+ breast cancers on the basis of the presence of defective ER is described as a tool potentially useful, as previously shown by the results of a pilot study, for predicting which among the ER+ tumors will respond and which will fail to repsond to hormonal modes of therapy. Improvements are introduced in the specimen sampling and ligand introduction steps of the immunohistochemical procedure which was developed for sub-classifying estrogen receptor-positive tumors of human breast cancers and other cancers of the estrogen target organs on the basis of the presence of defective estrogen receptors. Additionally, a new monoclonal antibody reagent which has potential use as a replacement for the polyclonal anti-ER antibody reagents is also described. The modified steps include the use of tumor imprints instead of cryosections; use of ligand coated slides instead of the original ligand layering step.

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. "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. The effective amounts of the complex are in the range of 10-600 micrograms for complexes comprising hsp7o, 50-1000 micrograms for hsp9o, and 10-600 micrograms for gp96.

Abstract: A therapeutic agent based on a recombinant adenovirus which employs an osteocalcin promoter for the expression of thymidine kinase can be administered intravascularly to treat metastatic cancer, including osteosarcoma, breast cancer, prostate cancer, ocular melanoma or brain cancer. Systemic administration of this agent provides a preferred route over previous disclosure of local direct administration. The same therapeutic agent can be effectively employed in the treatment of benign conditions, including benign prostatic hypertrophy and arteriosclerosis.

Abstract: The present invention relates to methods and compositions for enhancing immunological responses and for the prevention and treatment of infectious diseases or primary and metastatic neoplastic diseases based on the administration of macrophages and/or other antigen presenting cells (APC) sensitized with heat shock proteins non-covalently bound to peptide complexes and/or antigenic components. APC are incubated in the presence of hsp-peptide complexes and/or antigenic components in vitro. The sensitized cells are reinfused into the patient with or without treatment with cytokines including but not limited to interferon-.alpha., interferon-.alpha., interleukin-2, interleukin-4, interleukin-6 and tumor neurosis factor.

Abstract: The invention embodies the surprising discovery that Tissue Factor (TF) compositions and variants thereof specifically localize to the blood vessels within a vascularized tumor following systemic administration. The invention therefore provides methods and compositions comprising coagulant-deficient Tissue Factor for use in effecting specific coagulation and for use in tumor treatment. The TF compositions and methods of present invention may be used alone, as TF conjugates with improved half-life, or in combination with other agents, such as conventional chemotherapeutic drugs, targeted immunotoxins, targeted coaguligands, and/or in combination with Factor VIIa (FVIIa) or FVIIa activators.

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. "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. The effective amounts of the complex are in the range of 10-600 micrograms for complexes comprising hsp70, 50-1000 micrograms for hsp90, and 10-600 micrograms for gp96.

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. "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. The effective amounts of the complex are in the range of 10-600 micrograms for complexes comprising hsp70, 50-1000 micrograms for hsp90, and 10-600 micrograms for gp96.

Abstract: Polynucleotides encode soluble, multivalent molecular complexes which modify immune responses, and host cells comprise such polynucleotides. The molecular complexes comprise extracellular domains of transmembrane heterodimeric proteins, particularly T cell receptor and major histocompatibility complex proteins, which are covalently linked to the heavy and light chains of immunoglobulin molecules to provide soluble multivalent molecular complexes with high affinity for their cognate ligands. The molecular complexes can be used, inter alia, to detect and regulate antigen-specific T cells and as therapeutic agents for treating disorders involving immune system regulation, such as allergies, autoimmune diseases, tumors, infections, and transplant rejection.

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. "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. The effective amounts of the complex are in the range of 10-600 micrograms for complexes comprising hsp70, 50-1000 micrograms for hsp90, and 10-600 micrograms for gp96.

Abstract: Chimeric antibodies specific to human CD4 antigen, DNA encoding, pharmaceutical compositions containing and use thereof as therapeutic agents are taught. These chimeric antibodies contain Old World monkey variable sequences and human constant domain sequences, preferably human gamma 1, gamma 4 or mutated forms thereof. These antibodies possess desirable therapeutic properties including low antigenicity, reduced (or absent) T cell depleting activity, good affinity to human CD4 and enhanced stability (in vivo half-life).

Abstract: The invention embodies the surprising discovery that Tissue Factor (TF) compositions and variants thereof specifically localize to the blood vessels within a vascularized tumor following systemic administration. The invention therefore provides methods and compositions comprising coagulation-deficient Tissue Factor for use in effecting specific coagulation and for use in tumor treatment. The TF compositions and methods of present invention may be used alone, as TF conjugates with improved half-life, or in combination with other agents, such as conventional chemotherapeutic drugs, targeted immunotoxins, targeted coaguligands, and/or in combination with Factor VIIa (FVIIa) or FVII activators.

Abstract: The invention embodies the surprising discovery that Tissue Factor (TF) compositions and variants thereof specifically localize to the blood vessels within a vascularized tumor following systemic administration. The invention therefore provides methods and compositions comprising coagulation-deficient Tissue Factor for use in effecting specific coagulation and for use in tumor treatment. The TF compositions and methods of present invention may be used alone, as TF conjugates with improved half-life, or in combination with other agents, such as conventional chemotherapeutic drugs, targeted immunotoxins, targeted coaguligands, and/or in combination with Factor VIIa (FVIIa) or FVII activators.