Abstract: Compositions and methods for inducing cell membrane wounding, cell permeabilization and cell killing are provided. The composition comprises a polyvalent agent that binds to a highly expressed cell surface antigen present on the surface of a cell. Preferably, the cell surface antigen is associated with the cytoskeleton of the cell. A preferred polyvalent agent is an IgM, and enhanced cell wounding and killing can be provided by the addition of a crosslinking agent. At sublethal concentrations in vivo, the cell wounding antibodies permeabilize cells and dramatically enhance response to chemotherapeutic agents, even in patients refractory to the chemotherapeutic agents.

Abstract: The present disclosure relates to Cell Death Inducing Molecule (“CDIM”) binding proteins and pharmaceutical compositions thereof. Particularly, the disclosure provides CDIM binding proteins that are useful in the selective depleting and killing of B cells, including neoplastic B cells as well as neoplastic cells that are not of B-cell origin that express CDIM-like antigens. In addition, the disclosure encompasses polynucleotides encoding the disclosed antigen binding proteins, and expression systems for producing the same. Further the present disclosure encompasses methods of treating patients with B cell proliferative- and mediated diseases by administering the CDIM binding proteins as well as diagnostic assays for identifying proteins that bind to CDIM. The disclosure further contemplates diagnostic assays for identifying patient populations that can be treated with the CDIM binding proteins.

Abstract: The present disclosure relates to Cell Death Inducing Molecule (“CDIM”) binding proteins and pharmaceutical compositions thereof. Particularly, the disclosure provides CDIM binding proteins that are useful in the selective depleting and killing of B cells, including neoplastic B cells as well as neoplastic cells that are not of B-cell origin that express CDIM-like antigens. In addition, the disclosure encompasses polynucleotides encoding the disclosed antigen binding proteins, and expression systems for producing the same. Further the present disclosure encompasses methods of treating patients with B cell proliferative- and mediated diseases by administering the CDIM binding proteins as well as diagnostic assays for identifying proteins that bind to CDIM. The disclosure further contemplates diagnostic assays for identifying patient populations that can be treated with the CDIM binding proteins.

Abstract: Compositions and methods for inducing cell membrane wounding, cell permeabilization and cell killing are provided. The composition comprises a polyvalent agent that binds to a highly expressed cell surface antigen present on the surface of a cell. Preferably, the cell surface antigen is associated with the cytoskeleton of the cell. A preferred polyvalent agent is an IgM, and enhanced cell wounding and killing can be provided by the addition of a crosslinking agent. At sublethal concentrations in vivo, the cell wounding antibodies permeabilize cells and dramatically enhance response to chemotherapeutic agents, even in patients refractory to the chemotherapeutic agents.

Abstract: Formulations and methods of treating human patients suffering from a condition characterized by lymphoid cancer, autoimmune disease or B cell hyperproliferation are disclosed, the treatment comprising administering (1) a cytotoxic amount of an antibody having specific binding for CDIM epitopes on a B cell, and (2) a cytotoxic agent, including a chemotherapeutic agent, radioactive isotope, cytotoxic antibody, immunoconjugate, ligand conjugate, immunosuppressant, cell growth regulator and/or inhibitor, toxin, or mixtures thereof, including agents that disrupt the cytoskeleton of B cells, particularly vinca alkaloids or colchicine.

Abstract: Formulations and methods of treating human patients suffering from a condition characterized by lymphoid cancer, autoimmune disease or B cell hyperproliferation are disclosed, the treatment comprising administering (1) a cytotoxic amount of an antibody having specific binding for CDIM epitopes on a B cell, and (2) a cytotoxic agent, including a chemotherapeutic agent, radioactive isotope, cytotoxic antibody, immunoconjugate, ligand conjugate, immunosuppressant, cell growth regulator and/or inhibitor, toxin, or mixtures thereof, including agents that disrupt the cytoskeleton of B cells, particularly vinca alkaloids or colchicine.

Abstract: Methods are provided for inducing cell death in B-cells, including neoplastic B-cells, by employing reagents that bind to a B-cell epitope. Particularly, antibodies specific for the marker can be administered to a host to induce death in B-cells to which the antibodies bind or can be used in ex vivo clinical situations to selectively remove B-cells. A B-cell specific oligosaccharide epitope useful as a B-cell marker has been identified. The ligand being recognized on B lymphocytes has no apparent similarities to any of the known pan-B cells markers. In addition, proteins which specifically bind the disclosed epitope are provided. Human monoclonal antibody 216, which recognizes this B-cell epitope, is cytotoxic to B-cells and binds all CD19.sup.+ and CD20.sup.+ B lymphocytes in human peripheral blood and spleen. Furthermore, MAb 216 does not distinguish B cells by the isotype expressed, binding IgG.sup.+ and IgM.sup.+ cells with equal intensity, and also bind all B cells regardless of their CD5 expression.

Abstract: A method for separating nucleated fetal red blood cells and nucleated fetal cells and maternal granular sites from maternal blood is achieved by applying maternal blood to a triple gradient gel, isolating nucleated fetal cells from the gel and binding the isolated fetal cells to a solid support by means of an anti-i antibody bound to the solid support. The separated fetal cells can then be subjected to analysis for fetal sex or genetic disorders.

Abstract: A human monoclonal antibody, C5, specific for lipid A of the endotoxin core of Gram-negative bacteria and the hybridoma cell line which produces the antibody. The monoclonal antibody is produced by the fusion of lipid A sensitized lymphocytes and an appropriate fusion partner.

Abstract: Methods are provided for inducing cell death in B-cells, including neoplastic B-cells, by employing reagents that bind to a B-cell epitope. Particularly, antibodies specific for the marker can be administered to a host to induce death in B-cells to which the antibodies bind or can be used in ex vivo clinical situations to selectively remove B-cells. A B-cell specific oligosaccharide epitope useful as a B-cell marker has been identified. The ligand being recognized on B lymphocytes has no apparent similarities to any of the known pan-B cells markers. In addition, proteins which specifically bind the disclosed epitope are provided. Human monoclonal antibody 216, which recognizes this B-cell epitope, is cytotoxic to B-cells and binds all CD19.sup.+ and CD20.sup.+ B lymphocytes in human peripheral blood and spleen. Furthermore, MAb 216 does not distinguish B cells by the isotype expressed, binding IgG.sup.+ and IgM.sup.+ cells with equal intensity, and also bind all B cells regardless of their CD5 expression.

Abstract: This invention relates to methods, reagents and kits for detection of normal or ectopic pregnancy, the termination of pregnancy, or increased risk of preterm labor and rupture of membranes. Each embodiment involves sampling from the vaginal cavity, and determining the presence or absence of a specific analyte in the test sample. Sandwich or competition assay procedures can be used. Reagents and reagent kits for the above assays are included. The kit contains anti-(fetal fibronectin) antibody and an anti-fibronectin antibody.

Abstract: Nucleated fetal cells such as nucleated fetal red blood cells are separated from maternal blood with a discontinuous triple gradient gel and centrifugation. Nucleated fetal red blood cells are collected at an interface between a gel layer having a density in the range of from 1.105 to 1.110 g/mL and the second layer having a density in the range of from 1.075 to 1.085 g/mL, and maternal granulocytes are collected at an interface between a gel layer having a density in the range of from 1.115 to 1.125 g/mL and a layer having a density in the range of from 1.105 to 1.110 g/mL. This allows separation of fetal cells for testing from the maternal blood rather than the placenta or amniotic fluid, reducing the risk of sample collection and facilitating routine testing of fetal cells for evidence of genetic defects.

Abstract: A method for determining ectopic pregnancy in pregnant persons comprises obtaining a test sample; and determining the absence of a fetal restricted antigen in the sample. The sample is obtained from the vaginal cavity in the vicinity of the cervical canal or the cervical os. One fetal restricted antigen is fetal fibronectin. In one embodiment of this invention, the sample is contacted with an insoluble support to which anti-(fetal restricted antigen) antibody is adhered, and the fetal restricted antigen binding to the support is determined. Alternatively, a class of substances of which the fetal restricted antigen is a member is captured with a general binding antibody such as an anti-(fibronectin) antibody; an anti-(fetal restricted antigen) antibody such as anti-(fetal fibronectin) antibody is bound to the support; and the absence of binding with fetal restricted antigen is determined. Competition or sandwich assay procedures can be used. Reagents and reagent kits are also included.

Abstract: The invention provides a method for determining the presence of products of conception in a sample derived from the uterus during a D&C, or a therapeutic or spontaneous abortion, and comprises determining the presence in the sample of a fetal restricted antigen, which is found in products of conception but not found in significant amounts in maternal plasma or serum. Since the fetal restricted antigen is not present in significant quantities in maternal plasma or serum, the methods of this invention are reliable even when the sample is contaminated with maternal blood. One fetal restricted antigen is fetal fibronectin.In one embodiment of this invention, the sample is contacted with an insoluble support to which anti-(fetal restricted antigen) antibody is adhered, and the fetal restricted antigen binding to the support is determined.

Abstract: A method for determining normal intrauterine pregnancy during the first 20 weeks of pregnancy comprises obtaining a test sample; and determining the presence of a fetal restricted antigen in the sample. The test sample is removed the vaginal cavity in the vicinity of the cervical canal and/or the cervical os. One fetal restricted antigen is fetal fibronectin.In one embodiment of this invention, the test sample is contacted with an insoluble support to which anti-(fetal restricted antigen) antibody is adhered, and the fetal restricted antigen binding to the support is determined. Alternatively, the test sample is contacted with an insoluble support to which is adhered an antibody which binds a class of substances including the fetal restricted antigen; and the fetal restricted antigen binding to the support is determined. Reagents and reagent kits are also included.

Abstract: Novel adenocarcinoma binding human monoclonal antibody binds preferentially with ADCA antigens and is useful in diagnostic and imaging methods for identifying and locating adenocarcinoma cells, and in therapeutic methods to reduce the reproduction of adenocarcinoma cells. The novel ADCA antigen is useful in methods for diagnosing the presence of adenocarcinoma. The antigen, antibodies, hybridoma, reagents, therapeutic agents and methods of use are aspects of the invention.

Abstract: A method for determining increased risk of labor and fetal membrane rupture after week 20 of pregnancy comprises obtaining a secretion sample from the vaginal cavity; and determining the presence of a fetal restricted antigen in the sample. The sample can be removed from anywhere in the vaginal cavity, but is preferably removed from the posterior fornix or and/or cervical os. One fetal restricted antigen is fetal fibronectin. In one embodiment of this invention, the sample is contacted with an insoluble support to which anti-(fetal restricted antigen) antibody is adhered, and the fetal restricted antigen binding to the support is determined. Alternatively, the class of substances of which the fetal restricted antigen is a member is captured with a general binding antibody (such as anti-human fibronectin antibody), anti-(fetal restricted antigen) antibody (such as anti-fetal fibronectin antibody) is conjugated with the support, and binding with fetal restricted antigen is determined.

Abstract: Preeclampisa, pregnancy induced hypertension (PIH) and eclampsia are determined by identifying the presence of an endothelial cell marker in a sample of blood, plasma or serum of a pregnant woman using a sandwich or competition immunoassay. Cellular fibronectin marker in a sample is determined by binding with an anti-(cellular fibronectin) antibody. Reagents for these methods are also an aspect of the invention.

Abstract: Sensitive proteins in human biological secretion samples are preserved by dispersing them in an aqueous solution containing from 0.05 to 0.5M of a buffer which is effective to maintain the solution pH within the range of from 6.5 to 8.0; from 0.1 to 10 wt. % of a non-immune animal protein selected from the group consisting of albumin, ovalbumin, casein, glycoprotein and mixtures thereof; from 40 to 2000 kallikrein units/mL of an enzyme inhibitor of trypsin, chymotrypsin, kallikrein or plasmin; and from 0.01 to 0.1 wt. % of a bacteriostatic agent. The solution preferably also contains from 5 .mu.M to 1 mM of a protease inhibitor; and from 1 to 10 mM of a chelating agent. Optimally, the enzyme inhibitor is aprotinin, the protease inhibitor is phenylmethylsulfonylfluoride, the non-immune animal protein is bovine serum albumin, and the protease inhibitor is phenylmethylsulfonylfluoride. 0.0 to 0.15 mM of a water-soluble non-interfering salt, such as NaCl, may be desired.

Abstract: Methods are provided for producing fusion partners which involve employing an immortalized human myeloma cell line sensitive to HAT and having an additional dominant selectable resistance marker and fusing the doubly marked human myeloma cells with a stable immortalized rodent myeloma cell line, desirably previously subjected to substantial chromosome damage, and isolating cells having a substantially complete chromosomal complement of the rodent cell and at least about one chromosome of the human cell having a gene expressing said resistance, thereby being resistant to a selective agent. The resulting heteromyeloma may be fused with high efficiency with human lymphocytes to produce monoclonal antibodies.The cell lines designated as A6 and 36 were deposited at the A.T.C.C. on Jan. 11, 1983 and given accession numbers CRL8192 and CRL8193, respectively.