Abstract: The present invention includes fully human, neutralizing, monoclonal antibodies against human Insulin-like Growth Factor Receptor-I (IGFR1). The antibodies are useful for treating or preventing cancer in a subject. Also included are methods of using and producing the antibodies of the invention.

Abstract: The invention relates to novel hemoglobin compositions, particularly novel recombinant mutant hemoglobin compositions, which eliminate or substantially reduce 1) the creation of heart lesions, 2) gastrointestinal discomfort, 3) pressor effects, and 4) endotoxin hypersensitivity associated with the administration of extracellular hemoglobin compositions in various therapeutic applications. Applications described include treatments for anemia, head injury, hemorrhage or hypovolemia, ischemia, cachexia, sickle cell crisis and stroke; enhancing cancer treatments; stimulating hematopoiesis; improving repair of physically damaged tissues; alleviating cardiogenic shock; and shock resuscitation.

Abstract: A hemoglobin solution packaged in a flexible oxygen-impermeable container system. The container system includes a multi-layer film having at least a product contact layer, an oxygen and moisture barrier layer and an exterior layer. The flexible container system further includes an interface port for filling the flexible container with the hemoglobin solution and delivering the hemoglobin solution. The hemoglobin solution comprises a substantially stroma and tetramer free, cross linked, pyridoxylated hemoglobin solution including preservatives such as ascorbic acid, glycine and dextrose.

Abstract: The present invention relates to antibodies, antibody fragments, conjugates of antibodies and antibody fragments with cytotoxic agents, and hybridomas producing the antibodies and antibody fragments, where the antibodies and antibody fragments recognize extracellular epitopes of plasma membrane proteins that are not released into the extracellular fluid, and to methods for the detection, monitoring and treatment of malignancies such as breast cancer and ovarian cancer using the antibodies, antibody fragments and conjugates.

Abstract: Nitrosylhemoglobin can be produced by introducing gaseous NO into an aqueous solution of hemoglobin. It has been demonstrated that nitrosylhemoglobin in aqueous solution can be converted to SNO-hemoglobin upon introduction of oxygen to the solution, as is postulated to occur in the lungs. Nitrosylhemoglobin can be used in methods to produce the physiological effects of NO, for example, to reduce vasoconstriction and to inhibit platelet aggregation.

Abstract: The present invention provides methods for determining a ratio of an amount of a glycated form of a protein to a total amount of the protein in a sample containing the glycated protein, the glycosylated protein, or the glycoprotein. The method incorporates lateral flow test strip or vertical flow test strip devices having negatively charged carboxyl or carboxylate groups and hydroxyboryl groups immobilized and interspersed on a solid support matrix. The solid support matrix may include derivatives of cellulose (e.g., carboxy cellulose) derivatized with carboxylic acid (e.g., carboxylate, carboxyl) groups and hydroxyboryl compounds including phenylboronic acid (e.g., phenylborate), aminophenylboronic acid, boric acid (e.g., borate), or other boronic acid (e.g., boronate) compounds. The present invention is usefi.il for monitoring glycation or glycosylation of hemoglobin or albumin for monitoring glycemic control (e.g., glycemia in diabetes).

Abstract: Novel modified hemoglobins comprising polyalkylene glycols and novel methods for making those hemoglobins are provided. One group of modified hemoglobins comprise polyalkylene glycols bonded to the hemoglobin with an amide linkage at Glu-43(?). Additional polyalkylene glycols can also be bonded to the Glu-22(?) and/or the Asp-47(?). These hemoglobins are made by a novel amidation procedure. A second group of modified hemoglobins comprise a polyalkylene glycol covalently bonded to the hemoglobin at the ?-amino of a Val-1(?) or a Val-1(?). Additional polyalkylene glycols can optionally be covalently bonded to a limited number of ?-amino groups. This second group of hemoglobins is made using a novel reductive alkylation procedure. A third group of modified hemoglobins comprise a polyalkylene glycol bonded to a thiol group of the hemoglobin through a phenylsuccinimido linkage, wherein no polyalkylene glycol is bonded to a Cys-93(?).

Abstract: The present invention provides pegylated hemoglobins comprising a thiocarbamoyl-phenyl-polyethylene glycol (PEG) attached to hemoglobin, and comprising a polyethylene glycol (PEG) attached to hemoglobin by an acyl group. The invention also provides methods of preparing pegylated hemoglobins using isothiocyanato phenyl carbamate of PEG and using isothiocyanato phenyl di-PEG carbamate. The invention further provides compositions and blood substitutes comprising pegylated hemoglobins and methods of treating a subject which comprise administering to the subject blood substitutes comprising non-hypertensive pegylated hemoglobins.

Abstract: A stabilized hemoglobin solution is contacted with polymerizing agent. The stabilized hemoglobin solution includes stabilized tetrameric hemoglobin. At least a portion of the stabilized tetrameric hemoglobin is polymerized by reaction with the polymerizing agent, thereby producing a polymerized hemoglobin solution. In one embodiment, the stabilized hemoglobin solution includes a filtrate formed by filtrating polymerized solution of native hemoglobin through a filter having a molecular weight cut off of about 100 kD.

Abstract: A substantially tetramer free hemoglobin solution and a method for producing a substantially tetramer free hemoglobin solution. The method includes polymerizing a solution of hemoglobin, treating the polymerized hemoglobin solution to partially degrade the polymer to tetramer and removing tetramer from the hemoglobin solution.

Abstract: The present invention provides an isolated archael and bacterial heme binding protein which reversibly binds oxygen with a low affinity. The heme binding protein may be utilized as a blood substitute. The invention also provides a method for controlled storage of oxygen by contacting a bacterial heme binding protein with oxygen allowing the protein to bind and store oxygen. The also provides methods to sense gaseous ligands using the heme binding protein. In other embodiments, the invention provides chimeric proteins having a heme-binding domain of an isolated heme binding archael bacterial protein and a heterologous signaling domain.

Abstract: The invention describes methods for inhibiting angiogenesis in a tissue by administering an antagonist that specifically binds to a proteolyzed or denatured collagen but not to native triple helical forms of the collagen. Antagonists of the invention can target, for example, denatured collagens type-I, type-II, type-III, type-IV, type-V and combinations thereof. Methods utilizing such antagonists for therapeutic treatment of tumor growth, tumor metastasis or of restenosis also are described, as are methods to use such antagonists as diagnostic markers of angiogenesis in normal or diseased tissues both in vivo and ex vivo. Antagonists include monoclonal antibodies referred to as HUI77, HUIV26, and XL313.

Abstract: An improved method for producing human antibodies in SCID mice is provided. The improvement includes the use of dendritic cells pulsed with antigen-antibody complexes and antigen-antibody complexes as immunizing agents.

Abstract: Herein it is shown that hemoproteins (e.g., Ascaris hemoglobin, myoglobin, flavohemoglobins) have NO-consuming and deoxygenase activities. The invention provides a method of reducing the concentration of oxygen and/or nitric oxide in a mammal. The method of the invention comprises administering a therapeutically effective amount of a hemoprotein having NO-activated deoxygenase activity or an enzymatically active fragment thereof to a mammal. The method can be used to treat a mammal having pathologically proliferating cells, such as a tumor. In one embodiment, the hemoprotein is administered to reduce the oxygen concentration of a tumor. In another embodiment, the hemoprotein is administered together with a cytotoxic agent to treat a mammal having a tumor. The invention also provides a method of enzymatically generating toxic reactive oxygen species in a mammal for therapeutic purposes. The method comprises administering a therapeutically effective amount of a hemoprotein to a mammal.

Abstract: Glycosylphosphatidylinositol-(GPI-) anchored HSPG glypican-1 is strongly expressed in human breast and pancreatic cancer—both by the cancer cells and in the case of pancreatic cancer the adjacent fibroblasts—whereas expression of glypican-1 is low in the normal pancreas and in chronic pancreatitis. Treatment of two pancreatic cancer cell lines, which express glypican-1, with the enzyme phosphoinositide-specific phospholipase-C (PI-PLC) abrogated their mitogenic responses to two heparin-binding growth factors: fibroblast growth factor-2 (FGF2) and heparin-binding EGF-like growth factor (HB-EGF). Treatment of MDA-MB-231 and MDA-MB-468 breast cancer cells with PI-PLC abrogates the mitogenic response to two heparin-binding growth factors, heparin-binding epidermal growth factor-like growth factor (HB-EGF) and fibroblast growth factor-2 (FGF-2). Syndecan-1 is also expressed at high levels in breast cancer tissues as well as breast cancer cells by comparison with breast normal tissues.

Abstract: Compositions, and methods of use thereof, for use as blood substitute products comprise aqueous mixtures of oxygen-carrying and non-oxygen carrying plasma expanders and methods for the use thereof. The oxygen-carrying component may consist of any hemoglobin-based oxygen carrier, while the non-oxygen carrying plasma expander my consist of any suitable diluent.

Abstract: The present invention includes a method for diagnosing cancer comprising detecting the presence of survivin in the biological fluid of a patient. The present invention also provides kits comprising one or more agents that detect survivin polypeptide or survivin nucleic acid and a container for collecting biological fluid for testing.

Abstract: MK (midkine) was found to rise in the blood or urine of patients with various types of cancers at early stage. Based on this finding, a method for detecting early cancer, comprising the step of measuring MK in blood or urine was completed.

Abstract: The present invention comprises compounds, compositions thereof, and methods capable of delivering modified inositol hexaphospahte (IHP) comprising an internal pyrophosphate ring to the cytoplasm of mammalian cells. In certain embodiments, the present invention relates to compounds, compositions thereof, and methods that enhance the ability of mammalian red blood cells to deliver oxygen, by delivering IHP to the cytoplasm of the red blood cells.

Abstract: A polynucleotide sequence as shown in SEQ ID NO:1 is associated with metastatic potential of cancer cells, especially breast cancer cells. Methods are provided for determining the risk of metastasis of a tumor, by determining whether a tissue sample from a tumor expresses a polypeptide or mRNA encoded by a polynucleotide as shown in SEQ ID NO:1. Also provided are therapeutic methods and compositions.

Abstract: The present invention describes methods for inhibiting angiogenesis in tissues using vitronectin ?v?5 antagonists. The ?v?5-mediated angiogenesis is correlated with exposure to cytokines including vascular endothelial growth factor, transforming growth factor-? and epidermal growth factor. Inhibition of ?v?5-mediated angiogenesis is particularly preferred in vascular endothelial ocular neovascular diseases, in tumor growth and in inflammatory conditions, using therapeutic compositions containing ?v?5 antagonists.

Abstract: The invention relates to novel recombinant hemoglobins having reduced nitric oxide scavenging and/or increased high soluble expression. The invention further relates to methods of increasing the soluble expression of recombinant hemoglobin by adding exogenous hemin in molar excess of the heme binding sites of recombinant hemoglobin.

Abstract: Novel bipyridyl-osmium complex conjugates and their use in electrochemical assays are described. The redox reversible-osmium complexes can be prepared to exhibit unique reversible redox potentials and can thus be used in combination with other electroactive redox reversible species having redox potentials differing by at least 50 millivolts in electrochemical assays designed for use of multiple electroactive species in the same cell and in the same sample without interference between the two or more redox coupled conjugate systems.

Abstract: The invention relates to a method for preserving the stability of a hemoglobin blood substitute comprising maintaining the hemoglobin blood substitute in an atmosphere substantially free of oxygen. The method for preserving a deoxygenated hemoglobin blood substitute comprises maintaining the deoxygenated hemoglobin blood substitute in an oxygen barrier film overwrap package. In one embodiment, the package comprises a transparent laminate material comprising an oxygen barrier layer and a polyolefin layer, wherein the laminant has a thickness of between about 0.001 and about 0.01 inches (or about 0.0254 to about 0.254 millimeters) and an oxygen permeability of less than about 0.01 cubic centimeters per 100 square inches (or about 0.01 cc per 645 square centimeters) over 24 hours at 1 atmosphere and at about 23° C. The oxygen barrier layer comprises ethylene vinyl alcohol.

Abstract: The invention relates to a method for preserving the stability of a hemoglobin blood substitute comprising maintaining the hemoglobin blood substitute in an atmosphere substantially free of oxygen. The method for preserving the deoxygenated hemoglobin blood substitute comprises maintaining the deoxygenated blood substitute in an oxygen barrier film overwrap package, wherein at least one face of the overwrap package comprises a transparent laminate material and wherein at least one other face of the overwrap package comprises a foil laminate material. The preserved deoxygenated hemoglobin blood substitute comprises a deoxygenated hemoglobin blood substitute and an oxygen barrier film overwrap package wherein at least one face of the overwrap package comprises a transparent laminate material and wherein at least one other face of the overwrap package comprises a foil laminate material.

Abstract: The present invention employs a dissolved activated polyethylene glycol (aPEG) or related molecule that has been passed through a filtration means for the substantial reduction of bioburden or endotoxin levels in the aPEG solution. The resulting filtered aPEG solution can be used for the preparation of a PEGylated hemoglobin solution containing substantially reduced levels of bioburden or endotoxin.

Abstract: Nitrosylation of proteins and amino acid groups enables selective regulation of protein function, and also endows the proteins and amino acids with additional smooth muscle relaxant and platelet inhibitory capabilities. Thus, the invention relates to novel compounds achieved by nitrosylation of protein thiols. Such compounds include: S-nitroso-heme proteins, S-nitroso-t-PA, S-nitroso-cathepsin; S-nitroso-lipoproteins; and S-nitroso-immunoglobulins. The invention also relates to therapeutic use if S-nitroso-protein compounds for regulating protein function, cellular metabolism and effecting vasodilation, platelet inhibition, relaxation of non-vascular smooth muscle, and increasing blood oxygen transport by hemoglobin and myoglobin. The compounds are also used to deliver nitric oxide in its most bioactive form in order to achieve the effects described above, or for in vitro nitrosylation of molecules present in the body.

Abstract: This application describes the cloning of p63, a gene at chromosome 3q27-29, that bears homology to the tumor suppressor p53. The p63 gene encodes at least six different isotypes. p63 was detected in a variety of human and mouse tissue and demonstrates remarkably divergent activities, such as the ability to transactivate p53 reporter genes and induce apoptosis. Isotopes of p63 lacking a transactivation domain act as dominant negatives towards the transactivation by p53 and p63.

Abstract: The present invention provides DNA encoding a TADG-15 protein as well as a TADG-15 protein. Also provided is a vector capable of expressing the DNA of the present invention adapted for expression in a recombinant cell and regulatory elements necessary for expression of the DNA in the cell. The present invention further provides for methods of inhibiting TADG-15 expression and/or protease activity, methods of detecting TADG-15 mRNA and/or protein and methods of screening for TADG-15 inhibitors. Additionally, the present invention provides for cell-specific targeting via TADG-15 and methods of vaccinating an individual against TADG-15. The instant invention also includes a kit containing antibodies for the detection of TADG-15 protein. The methods described are useful in the diagnosis, treatment and prevention of cancer, particularly breast and ovarian cancer.

Abstract: Novel modified hemoglobins comprising polyalkylene glycols and novel methods for making those hemoglobins are provided. One group of modified hemoglobins comprise polyalkylene glycols bonded to the hemoglobin with an amide linkage at Glu-43(?). Additional polyalkylene glycols can also be bonded to the Glu-22(?) and/or the Asp-47(?). These hemoglobins are made by a novel amidation procedure. A second group of modified hemoglobins comprise a polyalkylene glycol covalently bonded to the hemoglobin at the ?-amino of a Val-1(?) or a Val-1(?). Additional polyalkylene glycols can optionally be covalently bonded to a limited number of ?-amino groups. This second group of hemoglobins is made using a novel reductive alkylation procedure. A third group of modified hemoglobins comprise a polyalkylene glycol bonded to a thiol group of the hemoglobin through a phenylsuccinimido linkage, wherein no polyalkylene glycol is bonded to a Cys-93(?).

Abstract: According to the claims, the present invention comprises the preparation of chemically modified, cross-linked hemoglobins with improved functional properties, the cross-linked hemoglobins prepared according to this method and the use of these hemoglobins as artificial oxygen carriers. The synthesis method is characterized by technical simplicity as well as by high yields. Deoxygenated hemoglobin of high purity is conjugated covalently under the protection of an antioxidant with an effector of oxygen binding, especially with pyridoxal-5-phosphate, after which the hemoglobin is polymerized with glutardialdehyde as a bifunctional cross-linking agent. At the same time, there is a large increase in the volume of the reaction mixture and a decrease in the concentration of the hemoglobin during the addition of the cross-linking agent. Subsequently, after further dilution with water, a polyethylene oxide derivative is chemically linked to the cross-linked hemoglobins.

Abstract: Red blood cells are purified by separating whole blood, such as by centrifugation, to form a red blood cell fraction and a liquid fraction. The whole blood can be defibrinated or treated to prevent coagulation prior to separation. Preferably, the whole blood is bovine blood. The red blood cell fraction is then diafiltered to purify the red blood cells. The purified red blood cells can then be lysed to form a lysate of purified red blood cells. The purified red blood cells and the lysate of purified red blood cells are suitable for use in producing hemoglobin blood substitute.

Abstract: Red blood cells are purified by defibrinating whole blood and then filtering the defibrinated whole blood, whereby at least a portion of a plasma component is separated from the red blood cells to form a suspension of red blood cells, thereby purifying the red blood cells. Whole blood is defibrinated by, for example, using a chemical coagulating agent or mechanical agitation. Separation of the plasma component from red blood cells can be completed by, for example, diafiltration. The suspension of red blood cells can then be employed to produce a hemoglobin-based oxygen carrier.

Abstract: The invention relates to covalently cross-linked mammalian hemoglobins, to which polyalkylene oxides are covalently linked. Such hemoglobins are surprisingly compatible with proteins of human and animal plasma, under all the possible conditions within the vascular system of the body. The invention furthermore relates to the production of these cross-linked hemoglobins linked with polyalkylene oxides, as well as to their use as artificial intravasal oxygen carriers in the human or animal organism or in individual organs.

Abstract: This invention provides a novel Fas antigen derivative which comprises at least a part or entire portion of Fas antigen extracellular region polypeptide in which at least one amino acid residue is deleted from a group of amino acid residues starting from the N-terminal amino acid residue of the Fas antigen polypeptide to a cysteine residue most close to the N-terminal side (excluding said cysteine residue), as well as a DNA fragment which encodes said Fas antigen derivative, a recombinant DNA molecule which contains said DNA sequence, a transformant in which said recombinant DNA molecule is introduced, a method for the production of said Fas antigen derivative, a medicament which contains said novel Fas antigen derivative as the active ingredient and a method for the improvement of activities and functions of Fas antigen and the like.

Abstract: A preparation is provided which can be injected or implanted into the human or animal body, and which comprises, as main component, globin that is insoluble at physiological pH, biocompatible and sterile.

Abstract: A method for producing haemin proteins by (i) inserting into plant cells one or more nucleic acid molecules that each comprise at least one sequence coding for a protein component of an animal haemin protein capable of reversibly binding oxygen, or for a variant or portion of said protein component, and optionally a sequence coding for a selection agent; (ii) selecting cells containing nucleic acid coding for the protein component of the haemin protein; (iii) optionally propagating the transformed cells either in a culture or by regenerating whole transgenic or chimeric plants; and (iv) recovering and optionally purifying a haemin protein that includes a complex consisting of the protein or proteins coded for by said nucleic acid and at least one iron-containing porphyritic nucleus, or a plurality of such complexes.

Abstract: An acellular red blood cell substitute which comprises an essentially tetramer-free, substantially stroma-free, cross-linked, polymerized, pyridoxylated hemoglobin and a nontoxic, pharmaceutically acceptable carrier, its use and a process for preparing said acellular red blood cell substitute.

Abstract: S-nitrosohemoglobin (SNO-Hb) can be formed by reaction of Hb with S-nitrosothiol and by other methods described herein which do not result in oxidation of the heme Fe. Other methods can be used which are not specific only for thiol groups, but which nitrosate Hb more extensively, and may produce polynitrosated metHb as a product or intermediate product of the method. SNO-Hb in its various forms and combinations thereof (oxy, deoxy, met; specifically S-nitrosylated, or nitrosated or nitrated to various extents) can be administered to an animal or human where it is desired to oxygenate, to scavenge free radicals, or to release NO+ groups to tissues. Thiols and/or NO donating agents can also be administered to enhance the transfer of NO+ groups. Examples of conditions to be treated by SNO-Hbs or other nitrosated or nitrated forms of Hb include ischemic injury, hypertension, angina, reperfusion injury and inflammation, and disorders characterized by thrombosis.

Abstract: Methods of using a complex (scuPA/suPAR) which has thrombolytic activity under physiological conditions and in the presence of IgG, or of at least one IgG-derived peptide, which complex comprises a single chain urokinase type plasminogen activator (scuPA) and a soluble urokinase plasminogen activator receptor (suPAR), for the treatment and/or prevention of thromboembolic disorders associated with the formation of fibrin clots are disclosed.

Abstract: Preventives and remedies for diffuse lung diseases whereby apoptosis can be inhibited and thus favorable preventive/therapeutic effects can be established. These drugs contain apoptosis-inhibiting substances as the active ingredient. The above apoptosis-inhibiting substances include Fas antagonists and Fas/Fas ligand binding inhibitors such as Fas derivatives and anti-Fas ligand antibodies.

Abstract: A non-pyrogenic, endotoxin-free, stroma-free, blood substitute capable of being used in humans or other mammals to provide oxygen to tissue and to deliver carbon dioxide to the lung and a process for its preparation are described.

Abstract: The present invention relates to nucleotide sequences, including expressed sequence tags (ESTs), oligonucleotide probes, polypeptides, antagonists and agonists vectors and host cells expressing, and immunoadhesions and antibodies to PRO201, PRO308 or PRO309 polypeptides. The invention further relates to compositions and method for the diagnosis and treatment of neoplastic cell growth and proliferation in mammals, including humans. The invention is based in part on the identification of genes that are amplified in the genome of tumor cells. Such gene amplification is expected to be associated with the overexpression of the gene product and contribute to tumorigenesis. Accordingly, the proteins encoded by the amplified genes are believed to be useful targents for the diagnosis and/or treatment (including prevention) of certain tumors (e.g., cancer) and may act as predictors of the prognosis of tumor treatment.

Abstract: Diseases which can be ameliorated by delivery of NO to tissues affected by the disease can be treated by administration of nitrosyl-heme-containing donors of NO, including nitrosylhemoglobin. Nitrosylhemoglobin can be made by the reaction of NO with hemoglobin under certain conditions in which the NO:hemoglobin ratio is critical, and is converted to SNO-Hb under physiological conditions.

Abstract: A method for conveniently detecting binding between the von Willebrand factor and glycoprotein Ib and a means to be used therein. The von Willebrand factor fixed in a reactor immobilized in a reaction vessel in the presence of bottrocetin is bound to a chimeric protein constructed by fusing the carboxyl terminal of a partial protein containing the von Willebrand factor-binding site of glycoprotein Ib with the amino terminal of the Fc region of an immunoglobulin molecule. Then the Fc region of the above immunoglobulin molecule is detected to thereby detect the binding between the von Willebrand factor and the glycoprotein Ib or inhibition of this binding.

Abstract: A novel gene (designated 158P1D7) and its encoded protein are described. While 158P1D7 exhibits tissue specific expression in normal adult tissue, it is aberrantly expressed in multiple cancers including set forth in Table 1. Consequently, 158P1D7 provides a diagnostic and/or therapeutic target for cancers. The 158P1D7 gene or fragment thereof, or its encoded protein or a fragment thereof, can be used to elicit an immune response.

Abstract: Nucleotide and amino acid sequences are provided for compounds which promote tissue growth, as well as methods for modulating tissue growth, for imaging tissues and organs, and for treating patients.

Abstract: Disclosed and claimed are methods for the isolation and use of stem cell inhibiting factors for regulating the abnormal stem cell cycle and for accelerating the post-chemotherapy peripheral blood cell recovery. Also disclosed and claimed are the inhibitors of stem cell proliferation.

Abstract: Nitric oxide (NO) interacts with hemoglobin (Hb) at its metal centers, whereas S-nitrosothiols (RSNOs) can donate the NO group to ?93 cysteine residues, thereby shielding the NO functionality from heme inactivation. S-nitrosylation of Hb is under the allosteric control of oxygen and the oxidation state of heme. NO group release from S-nitrosohemoglobin (SNO-Hb) is further facilitated by intracellular low molecular weight thiols, forming RSNOs which can be exported from the erythrocyte to regulate blood pressure. Hence, a dynamic cycle is established in which S-nitrosylation of Hb is initiated in the lung following oxygenation of red blood cells and is completed by SNO-Hb metabolism during arterial-venous transit. SNO-Hb can be formed by reaction of Hb with S-nitrosothiol. This procedure avoids oxidation of the heme.

Abstract: Isolated proteins comprising the T-cell surface antigen CD97 ? are provided. Compositions and methods for making and detecting CD97 ? are also provided. Further, the invention provides diagnostic and therapeutic methods and compositions for medical conditions involving CD97. The inventions also provides antibody compositions that bind specifically to CD97 ? subunits.