Abstract: Expression cassettes for enhanced expression and production of a polypeptide of interest in prokaryotic cells are provided. The expression cassettes provide for production of the polypeptide of interest so that such polypeptide can either be secreted from the host cell in an active conformation or conveniently processed and renatured to a functional state. Preferably, the polypeptide of interest is expressed as a fusion protein, particularly fused to a leader sequence from a highly expressed bacterial or bacteriophage gene. The polypeptide of interest may subsequently be cleaved from the leader sequence and refolded, or used as a fusion protein.

Abstract: A new B-cell receptor, Bp50, a 50 kilodalton polypeptide, that functions in B-cell proliferation is described. Ligands such as lymphokines, antibody molecules or the Fv fragments of antibody molecules that bind to Bp50 and augment the proliferation of activated B-cells can be used to regulate B-cell proliferation or differentiation.

Abstract: The present invention relates to methods which utilize anti-idiotypic antibodies, or fragments thereof, for tumor immunotherapy or immunoprophylaxis. Monoclonal anti-idiotypic antibodies which recognize an idiotype present on a second antibody or on a T lymphocyte or on an immune suppressor factor which is directed against a defined tumor antigen, can be used for immunization against a tumor, for immune anti-tumor activation or inhibition of suppression, or for in vitro activation of lymphocytes to be used in adoptive immunotherapy. The anti-idiotypic antibodies, or fragments thereof, can also be used to monitor anti-antibody induction in patients undergoing passive immunization to a tumor antigen by administration of anti-tumor antibody. In another embodiment, administration of T lymphocytes which express an idiotype directed against a defined tumor antigen can be used to transfer delayed-type hypersensitivity to the tumor.

Abstract: The present invention relates to methods of providing a targeted, amplified antitumor immune response using antibody-based fusion proteins. More specifically, the invention relates to the use of antibody-based fusion proteins comprising an immunoglobulin portion capable of binding to a tumor antigen linked to a biologically active lymphokine. The immunoglobulin portion targets the fusion protein to the site of the tumor cells and the lymphokine portion stimulates the proliferation of immune T cells at the site of the tumor cells, thereby amplifying the anti-tumor immune response. In preferred embodiments of the invention, the immunoglobulin portion of the fusion protein is derived from the L6 monoclonal antibody and/or the lymphokine is interleukin-2.

Abstract: The present invention relates to methods which utilize anti-idiotypic antibodies, or fragments thereof, for tumor immunotherapy or immunoprophylaxis. Monoclonal anti-idiotypic antibodies which recognize an idiotype present on a second antibody or on a T lymphocyte or on an immune suppressor factor which is directed against a defined tumor antigen, can be used for immunization against a tumor, for immune anti-tumor activation or inhibition of suppression, or for in vitro activation of lymphocytes to be used in adoptive immunotherapy. The anti-idiotypic antibodies, or fragments thereof, can also be used to monitor anti-antibody induction in patients undergoing passive immunization to a tumor antigen by administration of anti-tumor antibody. In another embodiment, administration of T lymphocytes which express an idiotype directed against a defined tumor antigen can be used to transfer delayed-type hypersensitivity to the tumor.

Abstract: Antiproliferative compositions are provided which are capable of sustained release of an antiproliferative agent, particularly a TGF-.beta., at a site proximal to a target cell. The compositions are effective in inhibiting proliferation of the target cell, particularly when used in combination with a vasoconstrictive agent.

Abstract: Thermally stable cytosine deaminase (CDase), and the gene coding therefor, is disclosed as well as methods of isolating, purifying, and recombinantly producing the same. The thermally stable CDase can be isolated from Saccharomyces cerevisiae. The yeast isolated enzyme has a molecular weight of approximately 32 kDa, as determined by gel filtration chromatography, and is composed of two subunits, each with a molecular weight of about 17 kDa. Thermally stable yeast CDase so purified shows no significant sequence homology with other known sequenced proteins.

Abstract: Type III TGF-.beta. receptor is identified in and purified from normal human embryonic palatal mesenchyme (HEPM) cells and the purified product characterized structurally and functionally. HEPM cells were found to express high levels of the type III TGF-.beta. receptor and were found to significantly down-regulate two classes of TGF-.beta. receptor binding site. Purification of the type III TGF-.beta. receptor from solubilized HEPM cell membranes by affinity chromatography yielded a biologically active protein of about 205 kd which specifically binds both the recombinant and natural forms of TGF-.beta.1 and TGF-.beta.2, with affinity dissociation constants in the picomolar range.

Abstract: The present invention relates to antibody-based fusion proteins wherein a portion of an immunoglobulin molecule is linked to a biologically active ligand. In particular embodiments of the invention, the fusion protein comprises a portion of an antibody which recognizes a cell surface antigen linked to a ligand which is a lymphokine or a cellular factor. A preferred embodiment of the fusion protein comprises the variable region of the anti-tumor monoclonal antibody L6 and an active lymphokine molecule such as IL-2. In another preferred embodiment of the present invention, the fusion protein comprises the variable region of the L6 monoclonal antibody and active platelet factor 4. The antibody-based fusion proteins of the invention may be used therapeutically to deliver biologically active ligands to a specific target cell or tissue.

Abstract: Peptides or proteins related to a melanoma associated antigen are described. These are produced in large quantities via recombinant DNA techniques and/or by chemical synthetic methods. The peptides or proteins can be used as immunogens in vaccine formulations which can induce an immune response that selectively destroys melanoma cells in a vaccinated individual. Where the peptides or proteins are expressed by a recombinant virus, inactivated or live virus vaccine formulations may be prepared.

Abstract: Novel polypeptide compositions are provided which inhibit human tumor cell growth, which may or may not stimulate autophosphorylation of pp6src and induce the release of a 52 kD polypeptide from neoplastic cells. Individual polypeptides may be isolated from mammalian blood platelets by selected extraction and purification procedures, may be synthesized or produced by hybrid DNA technology.

Abstract: A new B-cell receptor, Bp50, a 50 kilodalton polypeptide, that functions in B-cell proliferation is described. Ligands such as lymphokines, antibody molecules or the Fv fragments of antibody molecules that bind to Bp50 and augment the proliferation of activated B-cells can be used to regulate B-cell proliferation or differentiation.

Abstract: A chimeric transforming growth factor-beta termed TGF-.beta.1/.beta.2, a DNA molecule encoding TGF-.beta.1/.beta.2, a mammaliam cell transformed with said DNA molecule, and a method for producing chimeric TGF-.beta.1/.beta.2 are disclosed.

Abstract: The present invention relates to a novel monoclonal antibody reactive with human carcinoma cells. More particularly, the antibody of the invention is a monoclonal antibody reactive with a glycolipid cell membrane antigen on the surface of human carcinomas. The antibody displays a high degree of selectivity for carcinoma cells, showing a low degree of reactivity with certain normal human cells and no detectable reactivity with other types of tumors such as lymphomas, sarcomas or melanomas. In addition, the antibody of the invention is capable of internalizing within the carcinoma cells to which it binds and is therefore particularly useful for therapeutic applications, for example, as the antibody component of antibody-drug or antibody-toxin conjugates.

Abstract: The use of TGF-.beta. to inhibit HIV infection and/or replication is described. Both mature and precursor forms of TGF-.beta. are efficacious in inhibiting production of HIV. The TGF-.beta. used to inhibit HIV may be obtained from natural sources or may be produced by recombinant DNA or chemical synthetic techniques. TGF-.beta.1 and/or TGF-.beta.2 may be used. Additionally, hybrid TGF-.beta.1/.beta.2 molecules may also be utilized.

Abstract: cDNA clones coding for TGF-.beta.2 which are used to construct expression vectors capable of directing the high-level expression of mature, biologically active TGF-.beta.2, as well as precursor TGF-.beta.2 forms, in transfected Chinese Hamster Ovary cells (CHO cells) and transfected COS cells are described. CHO and COS transfectants secreting TGF-.beta.2 at high levels are also described. CHO cells transfected with a plasmid vector carrying the complete 414 amino acid simian TGF-.beta.2 precursor secrete approximately 5 .mu.g per ml culture media.

Abstract: A process for producing chimeric antibodies using novel recombinant DNA vectors and homologous recombination in vivo is described. The recombinant DNA constructs of the invention can be used to transfect antibody producing cells so that targeted homologous recombination occurs in the transfected cells leading to gene modification and the production of chimeric antibody molecules by the transfected cells.

Abstract: A process for producing chimeric antibodies using novel recombinant DNA vectors and homologous recombination in vivo is described. The recombinant DNA constructs of the invention can be used to transfect antibody producing cells so that targeted homologous recombination occurs in the transfected cells leading to gene modification and the production of chimeric antibody molecules by the transfected cells.

Abstract: The present invention is directed to the use of a recently discovered cytokine, Oncostatin M, to control endothelial cell immunogenicity, fibrinolytic activity and proliferation, and to its use in the treatment of a variety of human vascular and immune system disorders involving the vascular endothelium. The method of the invention includes the use of mature, hybrid, modified or truncated forms of Oncostatin M as well as Oncostatin M analogs. The invention is described by way of examples in which the efficacy of such compounds is evaluated using various in vitro assay systems.

Abstract: The present invention is concerned with novel monoclonal antibodies which bind strongly to a protein antigen associated with human non-small cell lung carcinomas ("NSCLC") human small cell lung carcinomas and certain other human carcinomas including many carcinomas of the colon and breast. The antibodies bind to normal human cells to a much lesser degree than to tumor cells. The antibodies find use both in diagnostic methods such as the detection of malignant cells associated with NSCLC and in therapeutic methods for treatment of human in NSCLC and certain other human carcinomas. Also disclosed is a novel 110,000 dalton glycoprotein antigen found on the cell surface of human non-small lung carcinoma tumor cells and on cells from certain other human cancers. The amino terminal amino acid sequence of this antigen is: ##STR1## in which X represents an unidentified amino acid.