Abstract: Cytotoxic biotherapeutic agents effective for treating certain types of cancer in humans are provided which comprise the TP-3 murine monoclonal antibody chemically conjugated to pokeweed antiviral protein (PAP). The invention further provides a method which utilizes the disclosed cytotoxic biotherapeutic agents to systemically treat cancer patients. With slight modifications the method of the present invention should be generally applicable to preparation and use of other cytotoxic biotherapeutic agents using chemical or recombinant derivatives of the TP-3 or TP-1 antibodies or PAP toxin. The invention is applicable to cancer patients who express the p80 antigen recognized by the TP-1/TP-3 antibodies either on the surface of their tumor cells or on the tumor blood vessels.

Abstract: The invention concerns the preparation and use of a live tumour-cell vaccine which contains three additional genes prepared by genetic-engineering techniques: a) a gene coding for a cell-surface protein with immunostimulatory activity, b) a cytokin gene and c) the thymidine kinase gene. The fields of application of the invention are medicine and genetic engineering. The live vaccine proposed owes its effect to the fact that a synergistic anti-tumour response is induced by the multiple transfer of genes which code for immunostimulatory activity. This leads to reliable repulsion of the vaccine cells and enables cells capable of multiplying to be injected as a vaccine. As an additional safety marker, the vaccine cells are given the thymidine kinase gene which enables the vaccine cells to be selectively killed in vivo.

Abstract: Disclosed are various compositions and methods for use in achieving specific blood coagulation. This is exemplified by the specific in vivo coagulation of tumor vasculature, causing tumor regression, through the site-specific delivery of a coagulant using a bispecific antibody.

Abstract: There is disclosed a method for treating an individual having a disease caused by cytokine-mediated toxicity comprising administering to the individual an effective amount of (a) an antibody that binds to an MIF polypeptide, wherein the MIF polypeptide has a molecular weight of about 12.5 kDa in combination with (b) anti-TNF.alpha., anti-IL1, anti-IFN-.gamma., IL-1RA, a steroid, a glucocorticoid, or IL-10.

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: Human gene GC6 is expressed more abundantly in senescent cells than young cells. Isolated, purified, and recombinant nucleic acids and proteins corresponding to the human GC6 gene and its mRNA and protein products, as well as peptides and antibodies corresponding to the GC6 protein can be used to identify senescent cells, distinguish between senescent and young cells, identify agents that alter senescent gene expression generally and GC6 expression specifically; such agents as well as GC6 gene and gene products and products corresponding thereto can be used to prevent and treat diseases and conditions relating to cell senescence.

Abstract: The present invention relates, in general, to a protein that regulates programmed cell death and, in particular, to the pro-apoptotic protein, Bax, which forms channels in lipid membranes. The invention further relates to methods of identifying agonists and antagonists of Bax channel formation and/or activity and thereby agents that can be used therapeutically to promote or inhibit cell death.

Abstract: The present invention relates to novel antibodies, antibody fragments and antibody conjugates and single-chain immunotoxins reactive with human carcinoma cells. More particularly, the antibodies, conjugates and single-chain immunotoxins of the invention include: a murine monoclonal antibody, BR96; a human/murine chimeric antibody, ChiBR96; a F(ab').sub.2 fragment of BR96; ChiBR96-PE, ChiBR96-LysPE40, ChiBR96 F(ab').sub.2 -LysPE40 and ChiBR96 Fab'-LysPE40 conjugates and recombinant BR96 sFv-PE40 immunotoxin. These molecules are reactive with a cell membrane antigen on the surface of human carcinomas. The BR96 antibody and its functional equivalents, displays a high degree of selectivity for carcinoma cells and possess the ability to mediate antibody-dependent cellular cytotoxicity and complement-dependent cytotoxicity activity.

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.

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 along with a cytokine 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: A compound comprises a target cell-specific portion, such as an antibody specific to tumor cell antigens, and an inactivating portion, such as an enzyme, capable of converting a substance which in its native state is able to inhibit the effect of a cytotoxic agent into a substance which has less effect against said cytotoxic agent. The prolonged action of a cytotoxic agent at tumor sites is therefore possible while protecting normal tissues from the effects of the cytotoxic agent.

Abstract: Specificity in immune responses is in part controlled by the selective interaction of T cell receptors with their cognate ligands, peptide/MHC molecules. The discriminating nature of this interaction makes these molecules, in soluble form, good candidates for selectively regulating immune responses. Attempts to exploit soluble analogs of these proteins has been hampered by the intrinsic low avidity of these molecules for their ligands. To increase the avidity of soluble analogs for their cognates to biologically relevant levels, divalent peptide/MHC complexes or T cell receptors (superdimers) were constructed. Using a recombinant DNA strategy, DNA encoding either the MHC class II/peptide or TCR heterodimers was ligated to DNA coding for murine Ig heavy and light chains. These constructs were subsequently expressed in a baculovirus expression system.

Abstract: The invention provides isolated nucleic acids molecules, designated Siva nucleic acid molecules, which encode proteins involved in immune cell apoptosis. The invention also provides antisense nucleic acid molecules, recombinant expression vectors containing Siva nucleic acid molecules, host cells into which the expression vectors have been introduced, and nonhuman transgenic animals in which a Siva gene has been introduced or disrupted. The invention still further provides isolated Siva proteins, fusion proteins, antigenic peptides and anti-Siva antibodies. Diagnostic, screening, and therapeutic methods utilizing compositions of the invention are also provided.

Abstract: Improved methods for the diagnosis and treatment of cancer which involve the targeting of slow-growing, relatively mutationally-spared cancer stemline are provided. These methods are an improvement over previous cancer detection and therapeutic methods because they provide for very early cancer detection and treatment and reduce the likelihood of clinical relapse after treatment.

Abstract: Antibodies that selectively bind to quadruplex nucleic acids are described. Isolated cells that produce such antibodies, and methods utilizing these antibodies, are also described.

Abstract: The invention relates to nucleic acid molecules coding for a tumor rejection antigen precursor. Specifically, the tumor rejection antigen precursor, or `TRAP", is processed into at least one tumor rejection antigen, which is presented by HLA-A2 molecules. Ramifications of the discovery are also set forth.

Abstract: The present invention relates to methods of treating or preventing cancer by administration of human chorionic gonadotropin, .beta.-human chorionic gonadotropin or a peptide containing a sequence of a portion of .beta.-human chorionic gonadotropin. In a preferred embodiment, the invention provides methods of treating or preventing Kaposi's Sarcoma, breast cancer or prostate cancer. in another preferred embodiment, the invention relates to .beta.-human chorionic gonadotropin peptides for treatment or prevention of cancer. The invention further provides assays for the utility of particular human chorionic gonadotropin preparations in the treatment or prevention of cancer. Pharmaceutical compositions and methods of administration are also provided.

Abstract: The present invention relates to methods of preparing a purified non-covalent heat shock protein 70-peptide complex capable of eliciting an immune response in a mammal comprising purifying heat shock protein 70-peptide complexes from mammalian tumor cells or mammalian cells infected with a virus, bacteria, or other infectious agent in the absence of ATP.

Abstract: A method for reducing the severity of host vs graft reaction (HVGR) by the transplant recipient of donor organ or tissue by the transplant recipient and is based on the discovery that hsp60 autoimmunity can function as an accelerator of foreign immunity and the down-regulation of hsp60 autoimmunity suppresses or prevents the graft rejection reaction. Administration of any composition which causes the down-regulation of hsp60 autoimmunity, such as hsp60 or peptide p277 in a tolerogenic carrier or a biologically active carrier capable of mediating a TH1.fwdarw.TH2 shift, will thus reduce the severity of HVGR.

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.