Abstract: The invention teaches methods for treating tumors and tumor metastases in a mammal comprising administering, to a mammal in need of treatment, a therapeutic amount of an antagonist sufficient to inhibit angiogenesis in combination with a therapeutic amount of anti-tumor immunotherapeutic agent, such as a anti-tumor antigen antibody/cytokine fusion protein having a cytokine and a recombinant immunoglobulin polypeptide chain sufficient to elicit a cytokine-specific biological response.

Abstract: Disclosed are compositions and methods for enhancing the circulating half-life of antibody-based fusion proteins. Disclosed methods and compositions rely on altering the amino acid sequence of the junction region between the antibody moiety and the fused protein moiety in an antibody-based fusion protein. An antibody-based fusion protein with an altered amino acid sequence in the junction region has a greater circulating half-life when administered to a mammal. Disclosed methods and compositions are particularly useful for reducing tumor size and metastasis in a mammal.

Abstract: Disclosed herein are methods and compositions for enhancing the immunogenicity of a preselected protein or peptide antigen in a mammal. Immunogenicity is enhanced by fusing the preselected antigen to an immunoglobulin heavy chain constant region to produce an Fc-antigen fusion protein. The Fc-antigen fusion proteins bind Fc receptors on the surface of antigen presenting cells, thereby targeting the antigen to the antigen presenting cells in the mammal. In addition, disclosed is a family of adjuvants, for example, an Fc-adjuvant fusion protein, for use in combination with the Fc-antigen fusion proteins to enhance or modulate a particular immune response against the preselected antigen.

Abstract: Disclosed are compositions and methods for producing fusion proteins with reduced immunogenicity. Fusion proteins of the invention include a junction region having an amino acid change that reduces the ability of a junctional epitope to bind to MHC Class II, thereby reducing its interaction with a T-cell receptor. Methods of the invention involve analyzing, changing, or modifying one or more amino acids in the junction region of a fusion protein in order to identify a T-cell epitope and reduce its ability to interact with a T cell receptor. Compositions and methods of the invention are useful in therapy.

Abstract: The invention provides a family of antibodies that specifically bind the human epithelial cell adhesion molecule. The antibodies comprise modified variable regions, more specially, modified framework regions, which reduce their immunogenicity when administered to a human. The antibodies, when coupled to the appropriate moiety, may be used in the diagnosis, prognosis and treatment of cancer.

Abstract: Disclosed are methods for producing fusion proteins with the heterodimeric cytokine, interleukin-12. In order to insure that the proper ratio of fused and non-fused subunits are obtained in the fusion protein, a specific stepwise approach to genetic engineering is used. This consists of first expressing the non-fused p40 IL-12 subunit in a production cell line, followed by or simultaneously expressing in the same cell, a second recombinant fusion protein consisting of the fused polypeptide linked by a peptide bond to the p35 subunit of IL-12. Molecules containing the p35 fusion protein cannot be secreted from the transfected mammalian cell without first complexing in a one to one ratio with the p40 subunit, thus ensuring the production of active heterodimeric fusion proteins.

Abstract: The invention provides a family of antibodies that specifically bind the human cell surface glycosphingolipid GD2. The antibodies comprise modified variable regions, more specially, modified framework regions, which reduce their immunogenicity when administered to a human. The antibodies may be coupled to a therapeutic agent and used in the treatment of cancer.

Abstract: Disclosed are compositions and methods for enhancing a cytocidal immune response directed against a preselected cell-type in a mammal. The methods and compositions rely on a combination of an antibody-cytokine immunoconjugate and an angiogenesis inhibitor. Once administered to the mammal, the immunoconjugate induces an immune response against the preselected cell-type, for example, a cancer cell which, as a result of the synergy with the angiogenesis inhibitor, is greater than the immune response induced by the immunoconjugate alone. The methods and compositions are particularly useful at killing solid tumors or virally-infected cells in a mammal.

Abstract: The invention relates to protein complexes and fusion proteins including at least two different cytokine molecules. The protein complexes and fusion proteins may further include a targeting moiety such as a region of an immunoglobulin. Methods of using the protein complexes and fusion proteins are also disclosed.

Abstract: Disclosed are nucleotide sequences, for example, DNA or RNA sequences, which encode an immunoglobulin Fc-Leptin fusion protein. The nucleotide sequences can be inserted into a suitable expression vector and expressed in mammalian cells. Also disclosed is a family of immunoglobulin Fc-Leptin fusion proteins that can be produced by expression of such nucleotide sequences. Also disclosed are methods using such nucleotide sequences and fusion proteins for treating conditions which are alleviated by the administration of leptin.

Abstract: Disclosed are compositions and methods for enhancing a cytocidal immune response directed against a preselected cell-type in a mammal. The methods and compositions rely on a combination of an antibody-cytokine immunoconjugate and an prostaglandin inhibitor. Once administered to the mammal, the immunoconjugate induces an immune response against the preselected cell-type, for example, a cancer cell which, as a result of immunopotentiation via the prostaglandin inhibitor, is greater than the immune response induced by the immunoconjugate alone. The methods and compositions are particularly useful at killing solid tumors or virally-infected cells in a mammal.

Abstract: The invention relates to protein complexes and fusion proteins including at least two different cytokine molecules. The protein complexes and fusion proteins may further include a targeting moiety such as a region of an immunoglobulin. Methods of using the protein complexes and fusion proteins are also disclosed.

Abstract: The invention provides cytokine fusion proteins with an increased therapeutic index, and methods to increase the therapeutic index of such fusion proteins. The fusion proteins of the invention are able to bind to more than one type of cytokine receptor expressed on cells and also bind to more than one cell type. In addition, the fusion proteins of the invention exhibit a longer circulating half-life in a patient's body than the corresponding naturally occurring cytokine.

Abstract: Disclosed are compositions and methods for producing fusion proteins with reduced immunogenicity. Fusion proteins of the invention include a junction region having an amino acid change that reduces the ability of a junctional epitope to bind to MHC Class II, thereby reducing its interaction with a T-cell receptor. Methods of the invention involve analyzing, changing, or modifying one or more amino acids in the junction region of a fusion protein in order to identify a T-cell epitope and reduce its ability to interact with a T cell receptor. Compositions and methods of the invention are useful in therapy.

Abstract: The invention provides a family of antibodies that specifically bind the human epithelial cell adhesion molecule. The antibodies comprise modified variable regions, more specially, modified framework regions, which reduce their immunogenicity when administered to a human. The antibodies, when coupled to the appropriate moiety, may be used in the diagnosis, prognosis and treatment of cancer.

Abstract: Disclosed are nucleotide sequences, for example, DNA or RNA sequences, which encode an immunoglobulin Fc-angiogenesis inhibitor fusion protein. The angiogenesis inhibitors can be angiostatin, endostatin, a plasminogen fragment having angiostatin activity, or a collagen XVIII fragment having endostatin activity. The nucleotide sequences can be inserted into a suitable expression vector and expressed in mammalian cells. Also disclosed is a family of immunoglobulin Fc-angiogenesis inhibitor fusion proteins that can be produced by expression of such nucleotide sequences. Also disclosed are methods using such nucleotide sequences and fusion proteins for treating conditions mediated by angiogenesis.

Abstract: Immunoconjugates for the selective delivery of a cytokine to a target cell are disclosed. The immunoconjugates are comprised of an immunoglobulin heavy chain having a specificity for the target cell, such as a cancer or virus-infected cell, and a cytokine, such as lymphotoxin, tumor necrosis factor alpha, interleukin-2, or granulocyte-macrophage colony stimulating factor, joined via Aits amino terminal amino acid to the carboxy-Aterminus of the immunoglobulin. Nucleic acid sequences encoding these immunoconjugates and methods of their preparation by genetic engineering techniques are also disclosed.

Abstract: Disclosed are methods and compositions for treating tumors. Disclosed methods and compositions enhance the uptake of immunocytokines into tumors, and are based on a combination of an immunocytokine with an immunocytokine uptake enhancing agent. Disclosed methods and compositions are particularly useful for reducing tumor size and metastasis in a mammal.

Abstract: Disclosed are methods and compositions for efficiently expressing antibody fusion proteins. Antibody fusion proteins of the invention include a hybrid antibody moiety containing sequences from more than one type of antibody and/or mutant antibody sequences. Hybrid antibody fusion proteins of the invention may be produced at high levels and may combine functional properties characteristic of different antibody types in addition to functional properties of a non-antibody moiety.

Abstract: Disclosed are methods for producing fusion proteins with the heterodimeric cytokine, interleukin-12. In order to insure that the proper ratio of fused and non-fused subunits are obtained in the fusion protein, a specific stepwise approach to genetic engineering is used. This consists of first expressing the non-fused p40 IL-12 subunit in a production cell line, followed by or simultaneously expressing in the same cell, a second recombinant fusion protein consisting of the fused polypeptide linked by a peptide bond to the p35 subunit of IL-12. Molecules containing the p35 fusion protein cannot be secreted from the transfected mammalian cell without first complexing in a one to one ratio with the p40 subunit, thus ensuring the production of active heterodimeric fusion proteins.