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: A method for treating serum samples to remove sialic acid from ligands to expose binding sites to enhance immunological binding, for use in assays and to generate novel anti-ligands is described. The method includes treatment of serum using neuraminidase.

Abstract: Novel compositions comprising Oncostatin M and congeners thereof, as well as methods for their preparation and methods for their use are provided. The compositions may be prepared by isolation from natural sources, or by recombinant means in either prokaryotic or eukaryotic host cells. In addition, the DNA and polypeptide sequences for Oncostatin M are disclosed. The compositions find use in modulating growth of cells, in particular inhibition of tumor cell proliferation, and stimulation of normal cell growth, especially cells involved in hematopoiesis. Cell growth inhibition compositions may additionally include an adjunctive agent comprising at least one of a transforming growth factor, tumor necrosis factor, or an interferon. Receptors having high affinity for Oncostatin M may additionally be used to screen polypeptides for Oncostatin M-like activity. Methods for use of antibodies to the compositions and probes specific for Oncostatin M mRNA as a means for detecting tumor cells are also provided.

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: The present invention relates to novel antibodies reactive with human carcinoma cells. More particularly, the antibodies of the invention include: a murine monoclonal antibody, BR96; a human/murine chimeric antibody, ChiBR96; and a F(ab').sub.2 fragment of BR96. These antibodies are reactive with a cell membrane antigen on the surface of human carcinomas. The antibodies display a high degree of selectivity for carcinoma cells and possess the ability to mediate ADCC and CDC activity. In addition, the antibodies of the invention internalize within the carcinoma cells to which they bind. The antibodies also have a unique feature in that they are cytotoxic when used in the unmodified form, at specified concentrations.

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: Novel compositions comprising Oncostatin M and congeners thereof, as well as methods for their preparation and methods for their use are provided. The compositions may be prepared by isolation from natural sources, or by recombinant means in either prokaryotic or eukaryotic host cells. In addition, the DNA and polypeptide sequences for Oncostatin M are disclosed. The compositions find use in modulating growth of cells, in particular inhibition of tumor cell proliferation, and stimulation of normal cell growth, especially cells involved in hematopoiesis. Cell growth inhibition compositions may additionally include an adjunctive agent comprising at least one of a transforming growth factor, tumor necrosis factor, or an interferon. Receptors having high affinity for Oncostatin M may additionally be used to screen polypeptides for Oncostatin M-like activity. Methods for use of antibodies to the compositions and probes specific for Oncostatin M mRNA as a means for detecting tumor cells are also provided.

Abstract: Novel compositions comprising Oncostatin M and congeners thereof, as well as methods for their preparation and methods for their use are provided. The compositions may be prepared by isolation from natural sources, or by recombinant means in either prokaryotic or eukaryotic host cells. In addition, the DNA and polypeptide sequences for Oncostatin M are disclosed. The compositions find use in modulating growth of cells, in particular inhibition of tumor cell proliferation, and stimulation of normal cell growth, especially cells involved in hematopoiesis. Cell growth inhibition compositions may additionally include an adjunctive agent comprising at least one of a transforming growth factor, tumor necrosis factor, or an interferon. Receptors having high affinity for Oncostatin M may additionally be used to screen polypeptides for Oncostatin M-like activity. Methods for use of antibodies to the compositions and probes specific for Oncostatin M mRNA as a means for detecting tumor cells are also provided.

Abstract: The present invention is concerned with novel monoclonal antibody L53 which binds strongly to a glycoprotein antigen associated with human tumors, including carcinomas of the colon, breast, and lung, as well as melanomas. The antibody binds to normal human cells to a much lesser degree than to tumor cells. The antibody finds use in diagnostic methods for as the detection of malignant cells associated with tumors. Also disclosed is a novel 70,000-75,000 dalton glycoprotein antigen recognized by MAb L53. The L53 antigen is found on the cell surface of human tumor cells. The amino terminal amino acid sequence of this antigen is: ##STR1## in which X represents an unidentified amino acid.

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: 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: 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.