Abstract: Disclosed is the surprising discovery that aminophospholipids, such as phosphatidylserine and phosphatidylethanolamine, are specific, accessible and stable markers of the luminal surface of tumor blood vessels. The present invention thus provides aminophospholipid-targeted diagnostic and therapeutic constructs for use in tumor intervention. Antibody-therapeutic agent conjugates and constructs that bind to aminophospholipids are particularly provided, as are methods of specifically delivering therapeutic agents, including toxins and coagulants, to the stably-expressed aminophospholipids of tumor blood vessels, thereby inducing thrombosis, necrosis and tumor regression.

Abstract: The present invention provides an anti-idiotypic monoclonal antibody which specifically induces an immune response against a glycosphingolipid. Additionally, this invention provides a method of producing the anti-idiotypic monoclonal antibody. Finally, this invention provides a composition of matter comprising an effective amount of a cytokine and a melanoma ganglio-side-specific antibody attached to a carrier.

Abstract: A peptide compound having the sequence Lys-Pro-Ser-Ser-Pro-Pro-Glu-Glu [SEQ ID NO:2] or a substitution variant, addition variant or other chemical derivative thereof inhibits cell invasion, endothelial tube formation or angiogenesis in vitro. A number of substitution variants and addition variants of this peptide, preferably capped at the N- and C-termini, as well as peptidomimetic derivatives, are useful for treating diseases and conditions mediated by undesired and uncontrolled cell invasion and/or angiogenesis. Pharmaceutical compositions comprising the above peptides and derivatives are administered to subjects in need of such treatment in a dosage sufficient to inhibit invasion and/or angiogenesis . The disclosed compositions and methods are particularly useful for suppressing the growth and metastasis of tumors.

Abstract: Superantigens, including Staphylococcal enterotoxins streptococcal pyrogenic exotoxins (SpE's), biologically active fragments and homologues thereof and fission proteins of the native superantigens, homologues and fragments, are useful agents for killing tumor cells, enhancing antitumor immunity and for treating tumors in a tumor-bearing subject. In particular, a subject having a tumor is treated with a tumoricidally effective amount of a superantigen, such as a SE or SpE, or a biologically active homologue thereof, fusion protein thereof or a fusion protein of the homologue. These agents stimulate T cells, leading to increased antitumor immunity and killing of tumor cells.

Abstract: A method for the early diagnosing of selected adenocarcinomas in a human comprising the steps of removing a bodily sample from the human, and assaying the bodily sample for elevated expression of a specific gene. The gene being assayed for in the, bodily sample is the TGFB-4 gene (hereinafter referred to as the endometrial bleeding associated factor (ebaf) gene. The bodily sample can be tissue from a specific organ in the body, or a blood sample. Increased levels of ebaf in the sample relative to basal levels may be indicative of a mucinous adenocarcinoma of the colon or ovaries, or an adenocarcinoma of the testis.

Abstract: This invention relates to compositions and methods comprising “lymphotoxin-&bgr; receptor blocking agents”, which block lymphotoxin-&bgr; receptor signalling. Lymphotoxin-&bgr; receptor blocking agents are useful for treating lymphocyte-mediated immunological diseases, and more particularly, for inhibiting Th1 cell-mediated immune responses. This invention relates to soluble forms of the lymphotoxin-&bgr; receptor extracellular domain that act as lymphotoxin-&bgr; receptor blocking agents. This invention also relates to the use of antibodies directed against either the lymphotoxin-&bgr; receptor or its ligand, surface lymphotoxin, that act as lymphotoxin-&bgr; receptor blocking agents. A novel screening method for selecting soluble receptors, antibodies and other agents that block LT-&bgr; receptor signalling is provided.

Abstract: The use of cognate heat shock protein 70-peptide complex to elicit an immune response against cancer and viral, bacterial and other infectious agents.

Abstract: A cell-free system based on the cytosol of normally growing cells, which reproduces measurable aspects of the apoptotic program, is provided. The apoptotic program is initiated by addition of DATP in the specific exemplification of the HeLa 100,000×g supernatant. Fractionation of the cytosol yielded a 15 kDa protein, identified by absorption spectrum and protein sequence as cytochrome c, that is required for in vitro apoptosis. Elimination of cytochrome c from cytosol by immunodepletion or inclusion of sucrose to stabilize mitochondria during cytosol preparation, diminished the apoptotic activity. Addition of exogenous cytochrome c to cytochrome c-depleted extracts restored apoptotic activity. Cells undergoing apoptosis in vivo showed increased release of cytochrome c to their cytosol, suggesting that mitochondria may function in apoptosis by releasing cytochrome c.

Abstract: This invention provides novel chimeric molecules that specifically binds a tumor cell bearing a c-erbB-2. The chimeric molecules comprise an effector molecule attached to a C6 antibody that specifically binds to c-erbB-2. The chimeric molecules can specifically target and deliver effector molecules to cells overexpressing c-erb-B2.

Abstract: Humanized antibodies are described which are specific to an Fc receptor (FcR). The humanized antibodies have at least a portion of a complementarity determining region (CDR) derived from a non-human antibody, e.g., murine, with the remaining portions being human in origin. The humanized antibodies can be used therapeutically as is or formulated as bifunctional molecules or immunotoxins.

Abstract: The invention relates to methods and compositions for the promotion of tissue repair. Specifically, compositions comprising heat shock proteins, including gp96, hsp90, and hsp70, uncomplexed or complexed noncovalently with antigenic molecules, are disclosed. Therapeutic methods for administering the hsp-containing compositions are disclosed. The disclosed methods are useful for promoting repair of tissues that were disrupted by a variety of causes including trauma (e.g., surgery, injury or burns) or disease or disorder (e.g., atherosclerosis and multiple sclerosis).

Abstract: Disclosed is a method for inhibiting the proliferation of a tumor in a mammal. The method involves the steps of (a) isolating a stress protein-peptide complex from tumor cells previously removed from the mammal and (b) administering the isolated stress protein-peptide complex back to the mammal in order to stimulate in the mammal an immune response against the tumor from which the complex was isolated. Stress protein-peptide complexes having particular utility in the practice of the instant invention include the Hsp70-peptide, Hsp90-peptide and gp96-peptide complexes.

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.

Abstract: The present invention relates to methods and compositions for the diagnosis, prevention, and treatment of tumors and cancers (e.g., colon cancer) in mammals, e.g., humans. The invention is based on the discovery of genes that ate differentially expressed in tumor cells relative to normal cells. The genes identified can be used diagnostically or as targets for therapy, and can be used to identify compounds useful in the diagnosis, prevention, and therapy of tumors and cancers.

Abstract: The invention provides a nucleic acid molecule which encodes the human NIM1 kinase. It also provides for the use of the nucleic acid molecule, fragments, variants and complements thereof and of the protein, portions thereof and antibodies thereto for characterization, diagnosis, evaluation, treatment, or prevention of disorders associated with expression. The invention additionally provides expression vectors and host cells for the production of the protein and a transgenic organism or model system.

Abstract: Extracellular domains of transmembrane heterodimeric proteins, particularly T cell receptor and major histocompatibility complex proteins, can be 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: Disclosed is a family of vaccines that contain stress protein-peptide complexes which when administered to a mammal are operative to initiate in the mammal a cytotoxic T cell response against cells infected with a preselected intracellular pathogen. Also disclosed are methodologies for preparing and administering vaccines containing such stress protein-peptide complexes.

Abstract: The invention provides the genomic sequence of GSSP-2, GSSP-2 cDNAs and GSSP-2 polypeptides. Further the invention provides polynucleotides including biallelic markers derived from the GSSP-2 gene and from genomic regions flanking the gene. This invention also provides polynucleotides and methods suitable for genotyping a nucleic acid molecule containing sample for one or more biallelic markers of the invention. Further, the invention provides methods to detect a statistical correlation between a biallelic marker allele and a phenotype and/or between a biallelic marker haplotype and a phenotype. The invention also concerns methods and compositions for killing neoplastic cells or inhibiting neoplastic cell growth. In particular, the present invention concerns cell proliferation arresting/inhibiting and apoptosis/necrosis inducing compositions and methods for the treatment of tumors. The present invention is directed to novel polypeptides and to nucleic acid molecules encoding those polypeptides.

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.

Abstract: The present invention provides methods for generating antigen-reactive T cells in vitro comprising priming immune cells and incubating the primed immune cells in vitro with a non-covalent complex of an heat shock protein and an antigenic molecule. The present invention further relates to methods for generating antigen-reactive CD4+ T cells for immunotherapy. Methods and compositions are also disclosed for the treatment and prevention of cancer or infectious disease in a subject comprising administering to the subject MHC matched antigen-reactive T cells that are generated in vitro by the present methods.