Abstract: Liposomal conjugates having a clinically useful delivery vehicle linked to a biologically active species which acts to increase vascular permeability and expand blood volume at or in proximity to the tumor site are disclosed. The vehicle-linked species may be, for example, a vasoactive agent, a substance that recruits or amplifies a vasoactive species, a drug, or a pharmaceutical compound. Suitable biological species comprises peptides, lipids, carbohydrates, or their derivatives. Chemical or recombinant DNA methods suitable for linking the species to the vehicles are indicated. A therapy is disclosed which comprises administering the vasoactive conjugate and delivering a diagnostic agent or a therapeutic agent at an optimal time thereafter, when tumor vasculature is maximally affected.

Abstract: A novel permeability enhancing peptide (PEP) is a fragment of interleukin-2. When joined to a delivery vehicle that can target a tumor site, the PEP can increase the subsequent uptake of antineoplastic or tumor imaging agents. The PEP can be chemically joined to a monoclonal antibody to form an immunoconjugate. Alternatively, an expression vector is genetically engineered to express a fusion protein. The fusion protein has an antigen-binding portion joined to the PEP. The PEP is most effective when it takes the form of a dimer, linked by a disulfide bridge. The PEP is substantially free of cytokine activity and produces minimal toxic side effects on normal tissues.

Abstract: A novel permeability enhancing peptide (PEP) is a fragment of interleukin-2. When joined to a delivery vehicle that can target a tumor site, the PEP can increase the subsequent uptake of antineoplastic or tumor imaging agents. The PEP can be chemically joined to a monoclonal antibody to form an immunoconjugate. Alternatively, an expression vector is genetically engineered to express a fusion protein. The fusion protein has an antigen-binding portion joined to the PEP. The PEP is most effective when it takes the form of a dimer, linked by a disulfide bridge. The PEP is substantially free of cytokine activity and produces minimal toxic side effects on normal tissues.

Abstract: Liposomal conjugates having a clinically useful delivery vehicle linked to a biologically active species which acts to increase vascular permeability and expand blood volume at or in proximity to the tumor site are disclosed. The vehicle-linked species may be, for example, a vasoactive agent, a substance that recruits or amplifies a vasoactive species, a drug, or a pharmaceutical compound. Suitable biological species comprises peptides, lipids, carbohydrates, or their derivatives. Chemical or recombinant DNA methods suitable for linking the species to the vehicles are indicated. A therapy is disclosed which comprises administering the vasoactive conjugate and delivering a diagnostic agent or a therapeutic agent at an optimal time thereafter, when tumor vasculature is maximally affected.

Abstract: Conjugates having a clinically useful delivery vehicle linked to a biologically active species which acts to increase vascular permeability and expand blood volume at or in proximity to the tumor site are disclosed. The vehicle-linked species may be, for example, a vasoactive agent, a substance that recruits or amplifies a vasoactive species, a drug, or a pharmaceutical compound. Suitable biological species comprises peptides, lipids, carbohydrates, or their derivatives. Chemical or recombinant DNA methods suitable for linking the species to the vehicles are indicated. A therapy is disclosed which comprises administering the vasoactive conjugate and delivering a diagnostic agent or a therapeutic agent at an optimal time thereafter, when tumor vasculature is maximally affected.

Abstract: Disclosed are methods for identifying the presence of a tumor in a mammal, comprising the steps of obtaining an antibody against cell ghosts, wherein the antibody is specific to an intracellular antigen not present on the cell surface of normal or neoplastic cells, and wherein the antibody is labeled with a label capable of being imaged; administering the antibody to the mammal, thereby permitting the antibody to bind preferentially to necrotic tissue; and imaging the binding of the antibody to the necrotic tissue, wherein a localized concentration of said antibody is indicative of the presence of a tumor. The antibodies used in these methods are preferably monoclonal antibodies, are also preferably specific for one or more nuclear proteins, and are also preferably labeled with one or more radionuclides. Also disclosed are antibodies for use with the foregoing methods.

Abstract: Disclosed is a method for measuring the effectiveness of therapy intended to kill malignant cells in vivo in a mammal, comprising the steps of obtaining monoclonal antibody that is specific to an internal cellular component of the mammal but not to external cellular components, wherein the monoclonal antibody is labeled; contacting the labeled antibody with tissue of a mammal that has received therapy to kill malignant cells in vivo, and determining the effectiveness of the therapy by measuring the binding of the labeled antibody to the internal cellular component. The internal cellular component is preferably insoluble intracellular antigen, and the label is preferably a radionuclide, a radiopaque material, or a magnetic resonance-enhancing material. Also disclosed is a method whereby the antibody to insoluble intracellular antigen is conjugated to an antineoplastic agent, so that upon administration of the antibody-antineoplastic agent conjugate, antineoplastic agent may be delivered to the tumor.

Abstract: Conjugates having a clinically useful delivery vehicle linked to a biologically active species which acts to increase vascular permeability and expand blood volume at or in proximity to the tumor site are disclosed. The vehicle-linked species may be, for example, a vasoactive agent, a substance that recruits or amplifies a vasoactive species, a drug, or a pharmaceutical compound. Suitable biological species comprises peptides, lipids, carbohydrates, or their derivatives. Chemical or recombinant DNA methods suitable for linking the species to the vehicles are indicated. A therapy is disclosed which comprises administering the vasoactive conjugate and delivering a diagnostic agent or a therapeutic agent at an optimal time thereafter, when tumor vasculature is maximally affected.

Abstract: A novel permeability enhancing peptide (PEP) is a fragment of interleukin-2. When joined to a delivery vehicle that can target a tumor site, the PEP can increase the subsequent uptake of antineoplastic or tumor imaging agents. The PEP can be chemically joined to a monoclonal antibody to form an immunoconjugate. Alternatively, an expression vector is genetically engineered to express a fusion protein. The fusion protein has an antigen-binding portion joined to the PEP. The PEP is most effective when it takes the form of a dimer, linked by a disulfide bridge. The PEP is substantially free of cytokine activity and produces minimal toxic side effects on normal tissues.

Abstract: Modified antibodies which have been by chemical conjugation with agents reactive with free amino groups are disclosed. Among the chemical agents disclosed for use in connection with the invention are heterobifunctional reagents and biotin. The use of these modified antibodies in the diagnosis and therapy of cancer and other mammalian disease is also disclosed. Diagnostic uses include immunoscintography. The modified antibodies may be further conjugated with labels or biologically active molecules for use in diagnosis and therapy. The modified antibodies may also be formulated into pharmaceutical compositions for these purposes.

Abstract: Disclosed is a method for measuring the effectiveness of therapy intended to kill malignant cells in vivo in a mammal, comprising the steps of obtaining monoclonal antibody that is specific to an internal cellular component of the mammal but not to external cellular components, wherein the monoclonal antibody is labeled; contacting the labeled antibody with tissue of a mammal that has received therapy to kill malignant cells in vivo, and determining the effectiveness of the therapy by measuring the binding of the labeled antibody to the internal cellular component. The internal cellular component is preferably insoluble intracellular antigen, and the label is preferably a radionuclide, a radiopaque material, or a magnetic resonance-enhancing material. Also disclosed is a method whereby the antibody to insoluble intracellular antigen is conjugated to an antineoplastic agent, so that upon administration of the antibody-antineoplastic agent conjugate, antineoplastic agent may be delivered to the tumor.

Abstract: Modified antibodies are disclosed which have been modified by chemical conjugation with a heterobifunctional reagent, such as SPDP. The use of these modified antibodies in the diagnosis and therapy of cancer and other mammalian disease is also disclosed. Diagnostic uses include immunoscintography. The modified antibodies may be further conjugated with labels or biologically active molecules for use in such diagnosis and therapy. The modified antibodies may also be formulated into pharmaceutical compositions for these purposes.

Abstract: Disclosed is a method for enhancing the effects of therapy that kills malignant cells in vivo comprising the steps of obtaining monoclonal antibody that is specific to an internal cellular component of a mammal but not to external cellular components, wherein the monoclonal antibody is attached to an antineoplastic agent; initiating therapy in a mammal to kill malignant cells in vivo, thereby causing some of the malignant cells to become necrotic; and administering the antibodies to the mammal. The antibodies bind to the necrotic malignant cells thereby delivering antineoplastic agent to surrounding cells. Also disclosed is a method of de novo therapy comprising administration of antibody-antineoplastic agent conjugate such that antineoplastic agent is delivered to the tumor. Also disclosed are antibodies for use with the foregoing methods and for use with diagnositc methods.

Abstract: Disclosed is a method for measuring the effectiveness of therapy intended to kill malignant cells in vivo in a mammal, comprising the steps of obtaining monoclonal antibody that is specific to an internal cellular component of the mammal but not to external cellular components, wherein the monoclonal antibody is labeled; contacting the labeled antibody with tissue of a mammal that has received therapy to kill malignant cells in vivo, and determining the effectiveness of the therapy by measuring the binding of the labeled antibody to the internal cellular component. The internal cellular component is preferably insoluble intracellular antigen, and the label is preferably a radionuclide, a radiopaque material, or a magnetic resonance-enhancing material. Also disclosed is a method whereby the antibody to insoluble intracellular antigen is conjugated to an antineoplastic agent, so that upon administration of the antibody-antineoplastic agent conjugate, antineoplastic agent may be delivered to the tumor.

Abstract: Hybridoma Lym-2 (ATCC No. HB 8613) produces murine IgGl monoclonal antibodies specifically against normal human B cells and derived malignancies. The Lym-2 antibodies have possible clinical utility for the in vivo diagnosis of human B-cell lymphomas and leukemias.

Abstract: Hybridoma Lym-1 (ATCC No. HB 8612) produces murine IgG2a monoclonal antibodies specifically against normal human B cells and derived malignancies. The Lym-1 antibodies have clinical utility for the in vivo diagnosis of human B-cell lymphomas and leukemias.