Abstract: The invention relates to monoclonal antibodies to the &agr;v&bgr;3 integrin receptor known to be expressed in large amounts on the surface of osteoclasts and accordingly, associated with bone resorption. The disclosed monoclonal antibodies are believed to recognize unique epitopes on &agr;v&bgr;3 and are useful in the treatment of conditions associated with excessive bone resorption and/or in the inhibition of tumor cell growth.

Abstract: A drug complex for delivery of a drug or other agent to a target cell, comprising a targeting carrier molecule which is selectively distributed to a specific cell type or tissue containing the specific cell type; a linker which is acted upon by a molecule which is present at an effective concentration in the environs of the specific cell type; and a drug or an agent to be delivered to the specific cell type. In particular, a drug complex for delivering a cytotoxic drug to prostate cancer cells, comprising a targeting carrier molecule which is selectively delivered to prostate tissue, bone or both; a peptide which is a substrate for prostate specific antigen; and a cytotoxic drug which is toxic to androgen independent prostate cancer cells.

Abstract: The invention describes the HLA class II binding peptides encoded by the MAGE-3 tumor associated gene, as well as nucleic acids encoding such peptides and antibodies relating thereto. The peptides stimulate the activity and proliferation of CD4+ T lymphocytes. Methods and products also are provided for diagnosing and treating conditions characterized by expression of the MAGE-3 gene.

Abstract: Multispecific molecules which target immune cells are disclosed. The molecules are “multispecific” because they bind to multiple (two or more), distinct targets, one of which is a molecule on the surface of an immune cell. Multispecific molecules of the invention include molecules comprised of at least one portion which binds to a molecule on an effector cell, such as an Fc receptor, and at least one portion (e.g., two, three, four or more portions) which binds to a different target, such as an antigen on a tumor cell or a pathogen. Multispecific molecules of the invention also include antigen “multimer complexes” comprised of multiple (i.e., two or more) portions which bind to a molecule on an antigen presenting cell (APC), such as an Fc receptor, linked to one or more antigens. These multimer complexes target antigens, such as self-antigens, to APCs to induce and/or enhance internalization (endocytosis), processing and/or presentation of the antigen by the APC.

Abstract: The invention relates to monoclonal antibodies to the &agr;v&bgr;3 integrin receptor known to be expressed in large amounts on the surface of osteoclasts and accordingly, associated with bone resorption. The disclosed monoclonal antibodies recognize unique epitopes on &agr;v&bgr;3 and are useful in the treatment of conditions associated with excessive bone resorption and/or in the inhibition of tumor cell growth.

Abstract: Methods and pharmaceutical compositions for modifying the immune response of a mammal to a specific antigen are provided. The methods include treating an antigen presenting cell to enhance expression of a major histocompatibility complex molecule and reacting the treated antigen presenting cell with the antigen extracorporeally to form an antigen-associated antigen presenting cell.

Abstract: Disclosed are antibodies that specifically recognize the new amino terminus of a protein cleaved by a protease during apoptosis. Methods of using and making the antibodies are also provided. The antibodies are particularly useful in methods of detecting apoptosis and testing candidate compounds for enhancing or inhibiting apoptosis.

Abstract: The invention provides a method of reducing the proliferation of a neoplastic cell. The method consists of contacting the neoplastic cell with a cytotoxic or cytostatic binding agent specifically reactive with an aberrantly expressed vesicular membrane associated neoplastic cell specific internalizing antigen. The neoplastic cell specific internalizing anitgen can be selected from the group consisting of lamp-2 and limp II families of lysosomal integral membrane proteins. Also provided is a method of intracellular targeting of a cytotoxic or cytostatic agent to a neoplastic cell population.

Abstract: The present invention relates to therapeutic methods and compositions employing superantigens. Methods and compositions employing superantigens and immunotherapeutic proteins in combination with one another have been found to provide more effective treatment than either component used alone. Superantigens, in conjunction with one or more additional immunotherapeutic antigens, may be used to either induce a therapeutic immune response directed against a target or to inhibit a disease causing immune response. Specific combinations of superantigens and immunotherapeutic antigens are used to treat specific diseases. The induction (or augmentation) of a desired immune against a target may be used, for example, to kill cancer cells or kill the cells or an infectious agent. The inhibition of an immune response, e.g., through the induction of T cell anergy, may be used to reduce the symptoms of an autoimmune disease.

Abstract: There is disclosed a method of preparing a vaccine suitable for administration to humans for the prevention or treatment of cancer. The vaccine is prepared by culturing human cancer cells in a serum-free medium and recovering from the culture medium the cell surface antigens shed from the human cancer cells during culturing. After purification, the collected or recovered shed antigens are employed to produce a vaccine consisting essentially of said antigens for the treatment or prevention of human cancer.

Abstract: Superantigens, including staphylococcal enterotoxins, are useful agents for killing tumor cells, enhancing antitumor immunity and treating cancer in a tumor-bearing host. Other useful superantigens include Streptococcal pyrogenic exotoxin, toxic shock syndrome toxins, mycoplasma antigens, mycobacteria antigens, minor lymphocyte stimulating antigens, heat shock proteins, stress peptides and derivatives thereof. The immune system of a subject with cancer is contacted with tumor cells that have been transfected with a nucleic acid encoding a superantigen or biologically active polypeptide of a superantigen. Alternatively, transfected accessory cells, inmunocytes or fibroblasts are used. Expression of the superantigen in the host induces T cell proliferation leading to increased antitumor immunity and tumor cell killing. The superantigen encoding nucleic acid may be administered to the tumor in vivo to transfect tumor cells, wherein superantigen expression induces a tumoricidal immune response.

Abstract: The invention is directed to methods for the creation and use of libraries of proteins which comprise polyclonal antibodies to a common antigen or group of antigens, receptor proteins with related variable regions, or other immune related proteins with variable regions. These polyclonal antibody libraries can be used to treat or prevent diseases and disorders including neoplasia such as cancer and other malignancies, parasitic infections, bacterial infections, viral infections and disorders such as genetic defects and deficiencies. Protein libraries may be patient-specific, disease-specific or both patient- and disease-specific. Libraries can also be used to detect a disease or disorder in a patient either by direct imaging or through the use of a diagnostic kit. The invention further includes novel cloning methods for the creation and transfer of nucleic acid sequences encoding protein variable regions and novel cloning vectors.

Abstract: A microsphere containing an immunogen bound to an inert particle having a mesh size of greater than about 35 mesh for site-specific release and induction of an immune response. The immune response may be an overall enhanced T lymphocyte immune response or a selective response. The physical and chemical characterigticg and/or modes of administration of the microsphere may be engineered to increase TH1 lymphocytes for treatment of cancer or infectious disease. The microencapsulated immunogen has an enteric coating for oral administration.

Abstract: The present invention combines physical and immunologic therapies for the treatment of neoplasms by conditioning a targeted neoplasm with an immunoadjuvant (also called immuno-modulator or immunopotentiator) and then physically destroying the conditioned neoplasm. A number of physical therapies can be used to achieve the physical destruction of the conditioned tumor mass.

Abstract: Disclosed is the surprising discovery that aminophospholipids, such as phosphatidylserine and phosphatidylethanolaminie, 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: A vaccine comprising a liposome preparation including at least one B-cell malignancy-associated antigen, IL-2, alone or in combination with at least one other cytokine, and at least one type of lipid molecule, is useful in a method of inducing humoral and cellular immune responses against malignant B-cells in a mammal.

Abstract: This invention relates to compositions and methods useful for activating LT-&bgr; receptor signaling, which in turn elicits potent anti-proliferative effects on tumor cells. More particularly, this invention relates to lymphotoxin heteromeric complexes formed between lymphotoxin-&agr; and multiple subunits of lymphotoxin-&bgr;, which induce cytotoxic effects on tumor cells in the presence of lymphotoxin-&bgr; receptor activating agents. Also within the scope of this invention are antibodies directed against the lymphotoxin-&bgr; receptor which act as lymphotoxin-&bgr; receptor activating agents alone or in combination with other lymphotoxin-&bgr; receptor activating agents either in the presence or absence of lymphotoxin-&agr;/&bgr; complexes. A screening method for selecting such antibodies is provided.

Abstract: The present invention provides a human selenium-binding protein (HSEBP) and polynucleotides which identify and encode HSEBP. The invention also provides genetically engineered expression vectors and host cells comprising the nucleic acid sequences encoding HSEBP and a method for producing HSEBP. The invention also provides for agonists and antibodies specifically binding HSEBP, and their use in the prevention and treatment of diseases associated with expression of HSEBP. Additionally, the invention provides for the use of antisense molecules to polynucleotides encoding HSEBP for the treatment of diseases associated with the expression of HSEBP. The invention also provides diagnostic assays which utilize the polynucleotide, or fragments or the complement thereof, and antibodies specifically binding HSEBP.

Abstract: This invention relates to a new member of a recently recognized TWIK potassium+channel family, herein identified as TASK, for TWIK-related acid-sensitive K+ channel. This is the first cloned mammalian channel that produces K+ currents that possesses all the characteristics of background conductances. The invention also relates to various constructs including the TASK or related human potassium channel family, and their uses.

Abstract: The invention presents methods for the treatment of symptoms associated with diseases states including cardiomyopathy, Parkinson's Disease and degenerative liver disease including cirrhosis comprising treatment with an effective amount of a composition comprising beta-amyloid, streptolysin O, and growth hormone.