Abstract: The invention provides compositions and methods of vaccination that enhance the potency of DNA vaccines. The immunogenic composition contains a DNA encoding a carboxyterminal fragment of a heat shock protein operably linked to a second DNA encoding a MHC class I restricted antigen.

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: Two novel mutant amyloid protein precursors (ABriPP and ADanPP) and their amyloid peptides (ABri and ADan) associated with Familial British Dementia and Familial Danish Dementia, respectively, are disclosed. Genetic constructs comprising DNA encoding these proteins is used to produced transgenic mammals that are useful models for neurological diseases associated with amyloid deposits, neurofibrillary tangles, non-neuritic plaques, neuronal degeneration and behavioral deficits characteristic of dementia and other symptoms of the human diseases. These models are used for testing potential therapeutic agents and methods. Also provided is a DNA-based test for detecting the mutations, the mutant proteins and peptides, antibodies specific for the proteins and peptides. Immunoassays permit detection of the mutant proteins, particularly in affected brain tissue, or detection of an antibody specific for a mutant peptide.

Abstract: Cyclic peptide compounds having 11 amino acids joined by a linking unit L, such that the linear dimension between the C&agr; carbon of the first amino acid and the C&agr; carbon of eleventh amino acid is between about 4 and 12 Ångstrom units; are useful for inhibiting the binding of uPA to the uPAR receptor. Methods for using the cyclic peptide compounds, and compositions containing them, for inhibiting the growth or metastasis of cancerous tumors are also disclosed.

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: 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: uPAR-targeting cyclic peptide compounds have 11 amino acids that correspond to human uPA(20-30) [SEQ ID NO:2], or are substitution variants at selected positions. The N and C terminal residues of these peptides are joined by a linking group L, so that the linear dimension between the a carbons of the first and the eleventh amino acids is between about 4 and 12 Ångstrom units. These cyclic peptides may be further conjugated to diagnostic labels or therapeutic moieties such as radionuclides. Such compounds are usefull for targeting uPAR expressed in pathological tissues and for inhibiting the binding of uPA to the uPAR. The pharmaceutical and therapeutic compositions inhibit cell migration, cell invasion, cell proliferation or angiogenesis, or induce apoptosis, and are thus useful for treating diseases or condition associated with undesired cell migration, invasion, proliferation, or angiogenesis, most notably cancer. The cyclic peptides are also used to detect and isolate cells expressing uPAR.

Abstract: A number of protein and glycoprotein antigens secreted by Mycobacterium. tuberculosis (Mt) have been identified as “early” Mt antigens on the basis early antibodies present in subjects infected with Mt prior to the development of detectable clinical disease. These early Mt antigens, in particular an 88 kDa secreted protein having a pI of about 5.2 present in Mt lipoarabinomannan-free culture filtrate, a protein characterized as Mt antigen 85C; a protein characterized as Mt antigen MPT51, a glycoprotein characterized as Mt antigen MPT32; and a 49 kDa protein having a pI of about 5.1, are useful in immunoassay methods for early, rapid detection of TB in a subject. Also provided are antigenic compositions, kits and methods to useful for detecting an early Mt antigen, an early Mt antibody, and immune complexes thereof.

Abstract: Superantigens, including staphylococcal enterotoxins, are useful agents in the killing of tumor cells, the enhancement of antitumor immunity and in the treatment of cancer in a tumor-bearing host. In particular, the immune system of a subject with cancer is contacted with tumor cells that have been transfected with nucleic acid encoding a superantigen or biologically active polypeptide of a superantigen. Alternatively, transfected accessory cells, immunocytes or fibroblasts are used. When the superantigen is expressed in the host, T cell proliferation is induced leading to increased antitumor immunity and tumor cell killing. The nucleic acid encoding a superantigen may be administered to the tumor in vivo to transfect tumor cells wherein superantigen expression induces a similar tumoricidal immune response.

Abstract: A method of stimulating a systemic immune response to a tumor cell or antigen associated with a pathogen by administering a mixture of a controlled release vehicle containing an immunopotentiating agent and antigen is described.

Abstract: The invention pertains to a method of treating or protecting against melanoma that comprises (a) obtaining a melanoma cell line that expresses one or more shared immunodominant melanoma antigens, (b) modifying the melanoma cell line to render it capable of producing an increased level of a cytokine relative to the unmodified cell line, and (c) administering the melanoma cell line to a mammalian host that has melanoma or is at risk for developing melanoma. Preferably the melanoma cell line is allogeneic and is not MHC-matched to the host.

Abstract: The 170 kDa adhesin subunit of the Entamoeba histolytica Gal/GalNAc adherence lectin is encoded by members of a gene family that includes hgl1, hgl2 and a newly discovered gene, hgl3. The DNA and encoded protein sequences of the hgl genes are disclosed. A number of proteins and peptide fragments of the adhesin as well as other functional derivatives, preferably produced by recombinant methods in prokaryotic cells are disclosed. A preferred peptide for a vaccine composition corresponds to amino acids 896-998 of the mature 170 kDa lectin and contains the galactose- and N-acetylgalactosamine-binding activity of the native lectin. These compositions are useful as immunogenic vaccine components and as diagnostic reagents. Methods are provided for a vaccine comprising one or more peptides of the lectin to immunize subjects at risk for infection by E. histolytica. Additionally, immunoassay methods are disclosed for measuring antibodies specific for an epitope of the lectin. These methods detect E.

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: Agonists of the adenosine A.sub.2 receptor promote the migration of endothelial cells, fibroblasts and epithelial cells. Thus, methods and pharmaceutical compositions useful for treating wounds and promoting wound healing comprise agents which cause stimulation of the adenosine A.sub.2 receptor, preferably receptor agonists and adenosine uptake blockers. Preferred agonists include 2-phenylaminoadenosine, 2-para-2-carboxyethylphenyl-amino-5'N-ethylcarboxamidoadenosine, 5'N-ethylcarbox-amidoadenosine, 5'N-cyclo-propyladenosine, 5'N-methylcarboxamidoadenosine and PD-125944. Preferred uptake blockers include dipyridamole, nitrobenzylthio-inosine, dilazep and R75231.

Abstract: Shigella IpaB protein or functional derivative binds to interleukin-1.beta.-converting enzyme (ICE) or an ICE homologue and activates a program of apoptosis. DNA encoding the Shigella IpaB protein, the IpaB protein or a functional derivative thereof is provided to a eukaryotic, preferably human, cell to induce apoptosis of that cell. This approach useful in treating diseases or disorders treatable by the eradication of unwanted cells, including cancer, autoimmunity, inflammation and chronic viral infections. Protein or peptide molecules (and the DNA coding therefor) which act as competitive antagonists for ICE binding without activating the apoptosis program are useful in treating or preventing diseases which involve an apoptotic mechanisms in their pathogenesis, for example AIDS, degenerative diseases such as Alzheimer's disease, myelodysplastic disorders, ischemic injuries or toxin-induced liver diseases.

Abstract: Cyclic peptide compounds having 11 amino acids joined by a linking unit L, such that the linear dimension between the C.sup..alpha. carbon of the first amino acid and the C.sup..alpha. carbon of eleventh amino acid is between about 4 and 12 .ANG.ngstrom units; are useful for inhibiting the binding of uPA to the uPAR receptor. Methods for using the cyclic peptide compounds, and compositions containing them, for inhibiting the growth or metastasis of cancerous tumors are also disclosed.