Abstract: Cell suicide (apoptosis) is associated with pathogenesis, for example, it is the major cause for the loss of neurons in Alzheimer's disease. Caspase-3 is critically involved in the pathway of apoptosis. Superantibody (SAT)-trans-membrane technology has been used to produce antibodies against the caspase enzyme in an effort to inhibit apoptosis in living cells. The advantage of using trans-membrane antibodies as apoptosis inhibitors is their specific target recognition in the cell and their lower toxicity compared to conventional apoptosis inhibitors. It is shown that a MTS-transport-peptide modified monoclonal anti-caspase-3 antibody reduces actinomycin D-induced apoptosis and cleavage of spectrin in living cells. These results indicate that antibodies conjugated to a membrane transporter peptide have a therapeutic potential to inhibit apoptosis in a variety of diseases.

Abstract: There is disclosed anti-receptor and growth blocking agents to the vitamin B12/transcobalamin II receptor and binding sites. The anti-receptor and growth blocking agents antagonize or modulate the vitamin B12/transcobalamin II receptor or binding sites, causing cellular depletion of vitamin B12, thus inhibiting cell division or causing apoptosis. Anti-receptor and growth blocking agents of the present invention include proteins (such as antibodies and antibody derivatives), peptides and small organic molecules. In a preferred embodiment, the anti-receptor agent is an antibody to the vitamin B12/transcobalamin II receptor.

Abstract: Vitamin B.sub.12 receptor modulating agents capable of modulating cell surface receptors by affecting the cell surface receptor trafficking pathway are disclosed. The vitamin B.sub.12 receptor modulating agents are comprised of a covalently bound rerouting moiety and targeting moiety linked by a water-solublizing linker.

Abstract: Receptor modulating agents capable of modulating cell surface receptors by affecting the cell surface receptor trafficking pathway are utilized for the treatment and diagnosis of a variety of disorders in warm-blooded animals, including neoplastic disorders. The receptor modulating agents are comprised of a covalently bound rerouting moiety and targeting moiety.

Abstract: Receptor modulating agents capable of modulating cell surface receptors by affecting the cell surface receptor trafficking pathway. The receptor modulating agents are comprised of a covalently bound rerouting moiety and targeting moiety.

Abstract: Vitamin B.sub.12 receptor modulating agents capable of modulating cell surface receptors by affecting the cell surface receptor trafficking pathway are disclosed. The vitamin B.sub.12 receptor modulating agents are comprised of a covalently bound rerouting moiety and targeting moiety linked by a water-solublizing linker.

Abstract: A biotinylated cobalamin, formed from a vitamin B.sub.12 molecule coupled to a biotin molecule, is disclosed. In a preferred embodiment, the vitamin B.sub.12 molecule is cyanocobalamin. The biotin molecule can also be coupled to a rerouting moiety, optionally through a biotin binding protein such as avidin or streptavidin. The biotinylated cobalamin binds to a cell surface receptor, is invaginated, and once internalized affects the receptor trafficking pathway.

Abstract: Targeting substance-diagnostic/therapeutic agent conjugates joined by stabilized Schiff base or hydrazone linkages are disclosed. In addition, slow release carrier-drug pharmaceuticals are described. The diagnostic and therapeutic conjugates and pharmaceuticals of the present invention provide certain advantages relating to in vivo administration, including controlled release of the active agent at a target site.

Abstract: The present invention involves a method of imaging tissue sites of inflammation which takes advantage of the up-regulation of surface antigenic markers on leukocytes upon activation thereof. A recognition agent selected from the group of chemotactic peptides, eosinophilic peptides and agents which are capable of selective interaction with a chemotactic receptor associated with activated leukocytes is radiolabeled. The radiolabeled recognition agent is infused into a patient and the patient's tissue sites are thereafter imaged in order to detect, evaluate or monitor tissue damage mediated by inflammation.

Abstract: Covalently-linked complexes (CLCs) for targeting a defined population of cells, comprising a targeting protein; a cytotoxic agent; and an enhancing moiety, wherein the enhancing moiety is capable of promoting CLC-target cell interaction are disclosed. Methods for using the claimed CLCs to obtain enhanced in vivo cytotoxicity and enhanced in vivo imaging are also described.

Abstract: Methods are disclosed for increasing the solubility of antibodies and their radioisotope, toxin, or drug immunoconjugates and for reducing the non-specific uptake of antibody, either conjugated or unconjugated, into the RES organs such as via Fc receptor-mediated mechanisms. The methods involve incubation of the reactive component with amphipathic molecules, such as an anionic detergent, to achieve the desired result. A preferred anionic detergent in this regard is sodium dodecylsulfate.

Abstract: Conjugates comprising a therapeutically effective proteinaceous active moiety linked to an albumin moiety which exhibit enhanced serum half-life and stability properties are disclosed. The conjugates may additionally comprise targeting moieties to facilitate selective localization of the active moiety at a target site. Conjugates of the present invention comprising an albumin moiety additionally exhibit reduced toxicity, yet maintain a high degree of selectivity and potency.

Abstract: The present invention involves methods of enhancing the amount of target site localization of lymphoid cells. Methods of the present invention take advantage of the up-regulation of surface antigenic markers on lymphoid cells upon activation thereof. Imaging and therapeutic applications of such enhancement are described.

Abstract: A method for enhancing production of antibodies through immunization with insolubilized immune complexes is disclosed. Purified antigen or heterogeneous antigen mixtures may be combined with polyclonal or monoclonal antibody and the resultant complex bound to an insolubilized matrix to form insolubilized immune complexes. Methods for improving the immunogenicity of a soluble antigen and for producing monoclonal anti-iodiotypic antibodies are also disclosed. Monoclonal antibodies that are specific for a distinct, as yet unrecognized epitope may be produced by another disclosed method . Insolubilized immune complexes, comprising antigen and antibody that is ether directly linked to Sepharose.RTM. or absorbed onto insolubilized protein A, and immunosorbents, comprising antibody absorbed onto insolubilized protein A, are also disclosed.

Abstract: The present invention involves method of enhancing the amount of label accumulating at tissue sites of inflammation. Methods of the present invention take advantage of the up-regulation of surface antigenic markers on leukocytes upon activation thereof. A method of imaging utilizing a chemotactic peptide containing an affinity label and a radionuclide label conjugated to leukocytes is taught. Imaging applications of such enhancement are described.