Abstract: Superantibodies having enhanced autophilic, catalytic, and/or membrane-penetrating properties are prepared by affinity-based conjugation of a photoactivatable organic molecule to a target immunoglobulin. The photoactivatable organic molecule bears a chromophoric aromatic hydrocarbon moiety, which has affinity for the immunoglobulin. Upon photolysis, the organic molecule is covalently linked to the immunoglobulin. A preferred organic molecule is a peptide and a preferred aromatic hydrocarbon moiety is a tryptophan residue. The photoactivatable organic molecule need not bear a purine, pyrimidine or azido group to effect binding to the immunoglobulin and/or photoactivation. Autophilic superantibodies can promote apoptosis of target cells and/or enhance therapeutic efficacies in the treatment of patients with diseases or disorders responsive to antibody therapy. Exemplary of such diseases are atherosclerosis and cardiovascular disease.

Abstract: Compositions and methods for providing antibodies having noncovalent, self-binding properties are disclosed. Such autophilic antibodies can bind cellular receptors to promote apoptosis of target cells and enhance therapeutic efficacies in the treatment of patients with debilitating or life-threatening diseases. Representative diseases targeted by the autophilic antibodies are lymphomas, breast cancers, colon cancers, and melanomas. Autoimmune disorders, Alzheimer's disease, and other neuro-degenerative conditions, as well as graft or transplant rejection, are among other treatable conditions.

Abstract: Compositions and methods for providing antibodies having noncovalent, self-binding properties are disclosed. Such autophilic antibodies can bind cellular receptors to promote apoptosis of target cells and enhance therapeutic efficacies in the treatment of patients with debilitating or life-threatening diseases. Representative diseases targeted by the autophilic antibodies are lymphomas, breast cancers, colon cancers, and melanomas. Autoimmune disorders, Alzheimer's disease, and other neuro-degenerative conditions, as well as graft or transplant rejection, are among other treatable conditions.

Abstract: Superantibodies having enhanced autophilic, catalytic, and/or membrane-penetrating properties are prepared by affinity-based conjugation of a photoactivatable organic molecule to a target immunoglobulin. The photoactivatable organic molecule bears a chromophoric aromatic hydrocarbon moiety, which has affinity for the immunoglobulin. Upon photolysis, the organic molecule is covalently linked to the immunoglobulin. A preferred organic molecule is a peptide and a preferred aromatic hydrocarbon moiety is a tryptophan residue. The photoactivatable organic molecule need not bear a purine, pyrimidine or azido group to effect binding to the immunoglobulin and/or photoactivation. The superantibodies can enhance the potency and expand the targeting range of target antibodies. Autophilic superantibodies can promote apoptosis of target cells and/or enhance therapeutic efficacies in the treatment of patients with diseases or disorders responsive to antibody therapy.

Abstract: There is disclosed charge-modified conjugates comprising a targeting protein bound to a therapeutic or diagnostic agent. Charge-modifying a conjugate to cause an acidic shift in the isoelectric point results in prolonged serum half-life upon in vivo administration and is useful to accumulate a therapeutic agent at the target site. Conversely, charge-modification to cause a basic shift in the isoelectric point of the conjugate reduces serum half-life upon in vivo use for diagnostic imaging purposes and results in higher target-to-background ratios.

Abstract: Polymeric carriers are polypeptides comprising at least one drug-binding domain that non-covalently binds a drug. A polymeric carrier may be attached to an antibody specific for desired target cells to form immunoconjugates that deliver a drug to the target cells in vivo. A polymeric carrier may be attached to a proteinaceous or a non-proteinaceous ligand or anti-ligand to form a conjugate useful in pretargeting protocols to deliver a drug to target cells in vivo. The carriers are derived from drug-binding proteins and produced through peptide synthesis or recombinant DNA technology.

Abstract: There is disclosed charge-modified conjugates comprising a targeting protein bound to a therapeutic or diagnostic agent. Charge-modifying a conjugate to cause an acidic shift in the isoelectric point results in prolonged serum half-life upon in vivo administration and is useful to accumulate a therapeutic agent at the target site. Conversely, charge-modification to cause a basic shift in the isoelectric point of the conjugate reduces serum half-life upon in vivo use for diagnostic imaging purposes and results in higher target-to-background ratios.

Abstract: Polymeric carriers are polypeptides comprising at least one drug-binding domain that non-covalently binds a drug. A polymeric carrier may be attached to an antibody specific for desired target cells to form immunoconjugates that deliver a drug to the target cells in vivo. The carriers are derived from drug-binding proteins and produced through peptide synthesis or recombinant DNA technology.

Abstract: There is disclosed an antibody and antibody-drug conjugate for targeting drug delivery as well as a class of chemicals, termed a drug-binding molecule of complementary structure (csDBM). The csDBM is designed to "fit" the drug by combining multiple non-covalent interactions between functional groups on the drug and opposing functional groups on the csDBM. The net result on the antibody-csDBM-drug conjugate is a drug stably bound to the csDBM so as not to dissociate during in vivo administration, but not so tightly bound to allow drug dissociation from the conjugate without significant loss of activity and retaining the drug's ability to bind to a higher affinity site on or within the target cell.

Abstract: Methods for improved targeting of antibody, antibody fragments, peptides hormones, steroid hormones and conjugates thereof are disclosed. Enhanced delivery to target cells of antibodies or fragments thereof or other receptor-mediated delivery system, such as peptide, specific for a population of cells of a mammal comprises steps of administering to said mammal an adequate dosage of blocking antibodies or fragments thereof or other receptor-mediated delivery system, such as peptide, and administering to said mammal an effective dosage of said antibodies or fragments thereof or other receptor-mediated delivery system, such as peptide, specific for said population of cells. In the preferred embodiment, the specific antibodies are monoclonal antibodies directed toward tumor-associated antigen in man.

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 insolubilized protein A to form insolubilized immune complexes. Methods for improving the immunogenicity of a soluble antigen and for producing monoclonal anti-idiotypic 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 either directly linked to Sepharose.RTM. or absorbed onto insolubolized protein A, and immunosorbents, comprising antibody absorbed onto insolubilized protein A, are also disclosed.

Abstract: Methods are disclosed for improving the efficiency of elicitation of monoclonal antibodies to glycoprotein antigens and tumor-associated antigens, and for inducing the production of IgG class monoclonal antibodies, in particular the IgG.sub.3 subclass. The methods involve the use of a lectin/extract immunogen to stimulate the production of the desired monoclonal antibodies.

Abstract: Methods for improved targeting of antibody, antibody fragments, peptides hormones, steroid hormones and conjugates thereof are disclosed. Enhanced delivery to target cells of antibodies or fragments thereof or other receptor-mediated delivery system, such as peptide, specific for a population of cells of a mammal comprises steps of administering to said mammal an adequate dosage of blocking antibodies or fragments thereof or other receptor-mediated delivery system, such as peptide, and administering to said mammal an effective dosage of said antibodies or fragments thereof or other receptor-mediated delivery system, such as peptide, specific for said population of cells. In the preferred embodiment, the specific antibodies are monoclonal antibodies directed toward tumor-associated antigen in man.